Breast Cancer

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

TOPLINE:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

For patients with early-stage ERBB2 (formerly HER2)–positive breast cancer, injections of increasing doses of autologous conventional type 1 dendritic cells (cDC1) combined with ERBB2-targeted antibodies demonstrate safety and effectiveness in enhancing immune response. The higher dose (100 million cells) shows enhanced immune effector recruitment and significant tumor regression before chemotherapy initiation.

METHODOLOGY:

• ERBB2-positive breast cancer survival has improved with anti-ERBB2 antibodies trastuzumab and pertuzumab, but for a pathologic complete response, chemotherapy remains necessary, which comes with significant toxic effects.
• A phase 1, nonrandomized clinical trial enrolled 12 patients with early-stage ERBB2-positive breast cancer in Tampa, Florida, from October 2021 to October 2022.
• Participants received intratumoral (IT) cDC1 injections weekly for 6 weeks at two dose levels (50 million cells for dose level 1 and 100 million cells for dose level 2), with six patients in each group.
• Starting from day 1 of the cDC1 injections, treatment included trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) administered intravenously every 3 weeks for six cycles, followed by paclitaxel (80 mg/m²) weekly for 12 weeks and surgery with lumpectomy or mastectomy.
• Primary outcomes measured safety and immune response of increasing doses of cDC1 combined with anti-ERBB2 antibodies before neoadjuvant chemotherapy; secondary outcomes assessed antitumor efficacy through breast MRI and residual cancer burden at surgery.

TAKEAWAY:

• IT delivery of ERBB2 cDC1 was safe and not associated with any dose-limiting toxic effects. The most frequent adverse events attributed to cDC1 were grade 1-2 chills (50%), fatigue (41.7%), headache (33%), and injection-site reactions (33%).
• Dose level 2 showed enhanced recruitment of adaptive CD3, CD4, and CD8 T cells and B cells within the tumor microenvironment (TME), along with increased innate gamma delta T cells and natural killer T cells.
• Breast MRI revealed nine objective responses, including six partial responses and three complete responses, with three cases of stable disease.
• Following surgery, 7 of 12 patients (58%) achieved a pathologic complete response, including all 3 hormone receptor–negative patients and 4 of the 9 hormone receptor–positive patients.

IN PRACTICE:

“Overall, the clinical data shown here demonstrate the effects of combining ERBB2 antibodies with IT [intratumoral] delivery of targeted cDC1 to enhance immune cell infiltration within the TME [tumor microenvironment] and subsequently induce tumor regression before chemotherapy,” wrote the authors, who noted they will be testing the higher dose for an ongoing phase 2 trial with an additional 41 patients.

SOURCE:

The study was led by Hyo S. Han, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. It was published online on December 5, 2024, in JAMA Oncology.

LIMITATIONS:

Because only two dose levels of cDC1 were tested, it remains unclear whether higher doses or different administration schedules could further enhance immune response. Additionally, the nonrandomized design prevents definitive conclusions about whether the clinical benefits were solely from the anti-ERBB2 antibodies. The small sample size also makes it difficult to determine if the pathologic complete responses were primarily due to the 12 weeks of trastuzumab/pertuzumab/paclitaxel treatment.

DISCLOSURES:

This study was funded by the Moffitt Breast Cancer Research Fund, Shula Fund, and Pennies in Action. Several authors reported research support and personal and consulting fees from US funding agencies and multiple pharmaceutical companies outside of the submitted work, as well as related intellectual property and patents.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — Canadian women aged 40-49 years at no or moderate risk for breast cancer who participated in organized mammography screening programs had a significantly greater breast cancer 10-year net survival than that of similar women who did not participate in such programs, according to data presented here at the Family Medicine Forum 2024. 

The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.

 

Overdiagnosis Challenged

Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.

“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization. 

To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them. 

“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.

Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths). 

Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%). 

The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).

Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.

Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”

 

Modeling Shows Little Screening Benefit

The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.

Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.

The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.

Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.

It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.

Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years. 

The study was supported by the University of Ottawa’s department of family medicine. 

Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — Canadian women aged 40-49 years at no or moderate risk for breast cancer who participated in organized mammography screening programs had a significantly greater breast cancer 10-year net survival than that of similar women who did not participate in such programs, according to data presented here at the Family Medicine Forum 2024. 

The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.

 

Overdiagnosis Challenged

Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.

“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization. 

To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them. 

“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.

Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths). 

Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%). 

The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).

Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.

Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”

 

Modeling Shows Little Screening Benefit

The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.

Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.

The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.

Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.

It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.

Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years. 

The study was supported by the University of Ottawa’s department of family medicine. 

Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

VANCOUVER, BRITISH COLUMBIA — Canadian women aged 40-49 years at no or moderate risk for breast cancer who participated in organized mammography screening programs had a significantly greater breast cancer 10-year net survival than that of similar women who did not participate in such programs, according to data presented here at the Family Medicine Forum 2024. 

The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.

 

Overdiagnosis Challenged

Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.

“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization. 

To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them. 

“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.

Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths). 

Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%). 

The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).

Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.

Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”

 

Modeling Shows Little Screening Benefit

The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.

Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.

The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.

Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.

It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.

Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years. 

The study was supported by the University of Ottawa’s department of family medicine. 

Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

At 1 year, 82% of patients with breast cancer who received a 1-week ultrahypofractionated breast radiotherapy regimen reported no or mild toxicities. Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.

METHODOLOGY:

• In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
• In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
• Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
• Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
• Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.

TAKEAWAY:

• Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
• At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
• Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
• Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.

IN PRACTICE:

“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”

SOURCE:

The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.

LIMITATIONS:

The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.

DISCLOSURES:

Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.