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FDA Approves Pluvicto for Earlier Use in PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
The United States Food and Drug Administration (FDA) has expanded the approval for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis) to include adults with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), who have received androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
The radioligand therapeutic agent was previously approved for the treatment of PSMA-positive mCRPC in patients who have already received ARPI therapy and taxane-based chemotherapy. Approval for the expanded indication was based on efficacy demonstrated in the randomized, open-label, phase 3 PSMAfore trial.
Treatment in 468 patients who progressed on one ARPI and who were deemed appropriate for delay of taxane-based chemotherapy was associated with improved radiographic progression-free survival (rPFS) and overall survival (OS) vs a different ARPI.
Patients were randomized 1:1 to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for six doses) or to receive a different ARPI, according to a statement from the FDA. Those who progressed on the new ARPI were allowed to cross over to the experimental therapy arm after progression, and 60% did so.
Median rPFS was 9.3 vs 5.6 months in the experimental and control arms, respectively (hazard ratio [HR], 0.41). Median OS durations were 24.5 and 23.1 months, respectively (HR, 0.91), but the difference in OS did not reach statistical significance.
Adverse reactions were consistent with the known safety profile of lutetium Lu 177 vipivotide tetraxetan, which includes possible radiation exposure, myelosuppression, and renal toxicity.
The recommended dose, according to prescribing information, is 7.4 GBq (200 mCi) administered intravenously every 6 weeks for six doses or until disease progression or unacceptable toxicity.
“The earlier indication for Pluvicto could really change our treatment paradigms for patients with mCRPC. It offers a targeted therapy that better delays disease progression compared to a second ARPI,” Michael Morris, MD, of Memorial Sloan Kettering Cancer Center, New York, and the principal investigator of the study in the United States stated in a Novartis press release. “This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one ARPI and has not received chemotherapy.”
A version of this article first appeared on Medscape.com.
The United States Food and Drug Administration (FDA) has expanded the approval for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis) to include adults with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), who have received androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
The radioligand therapeutic agent was previously approved for the treatment of PSMA-positive mCRPC in patients who have already received ARPI therapy and taxane-based chemotherapy. Approval for the expanded indication was based on efficacy demonstrated in the randomized, open-label, phase 3 PSMAfore trial.
Treatment in 468 patients who progressed on one ARPI and who were deemed appropriate for delay of taxane-based chemotherapy was associated with improved radiographic progression-free survival (rPFS) and overall survival (OS) vs a different ARPI.
Patients were randomized 1:1 to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for six doses) or to receive a different ARPI, according to a statement from the FDA. Those who progressed on the new ARPI were allowed to cross over to the experimental therapy arm after progression, and 60% did so.
Median rPFS was 9.3 vs 5.6 months in the experimental and control arms, respectively (hazard ratio [HR], 0.41). Median OS durations were 24.5 and 23.1 months, respectively (HR, 0.91), but the difference in OS did not reach statistical significance.
Adverse reactions were consistent with the known safety profile of lutetium Lu 177 vipivotide tetraxetan, which includes possible radiation exposure, myelosuppression, and renal toxicity.
The recommended dose, according to prescribing information, is 7.4 GBq (200 mCi) administered intravenously every 6 weeks for six doses or until disease progression or unacceptable toxicity.
“The earlier indication for Pluvicto could really change our treatment paradigms for patients with mCRPC. It offers a targeted therapy that better delays disease progression compared to a second ARPI,” Michael Morris, MD, of Memorial Sloan Kettering Cancer Center, New York, and the principal investigator of the study in the United States stated in a Novartis press release. “This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one ARPI and has not received chemotherapy.”
A version of this article first appeared on Medscape.com.
The United States Food and Drug Administration (FDA) has expanded the approval for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis) to include adults with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), who have received androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
The radioligand therapeutic agent was previously approved for the treatment of PSMA-positive mCRPC in patients who have already received ARPI therapy and taxane-based chemotherapy. Approval for the expanded indication was based on efficacy demonstrated in the randomized, open-label, phase 3 PSMAfore trial.
Treatment in 468 patients who progressed on one ARPI and who were deemed appropriate for delay of taxane-based chemotherapy was associated with improved radiographic progression-free survival (rPFS) and overall survival (OS) vs a different ARPI.
Patients were randomized 1:1 to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for six doses) or to receive a different ARPI, according to a statement from the FDA. Those who progressed on the new ARPI were allowed to cross over to the experimental therapy arm after progression, and 60% did so.
Median rPFS was 9.3 vs 5.6 months in the experimental and control arms, respectively (hazard ratio [HR], 0.41). Median OS durations were 24.5 and 23.1 months, respectively (HR, 0.91), but the difference in OS did not reach statistical significance.
Adverse reactions were consistent with the known safety profile of lutetium Lu 177 vipivotide tetraxetan, which includes possible radiation exposure, myelosuppression, and renal toxicity.
The recommended dose, according to prescribing information, is 7.4 GBq (200 mCi) administered intravenously every 6 weeks for six doses or until disease progression or unacceptable toxicity.
“The earlier indication for Pluvicto could really change our treatment paradigms for patients with mCRPC. It offers a targeted therapy that better delays disease progression compared to a second ARPI,” Michael Morris, MD, of Memorial Sloan Kettering Cancer Center, New York, and the principal investigator of the study in the United States stated in a Novartis press release. “This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one ARPI and has not received chemotherapy.”
A version of this article first appeared on Medscape.com.
3D Total Body Photography Shown to Decrease Biopsies, Improve Dx of Nonmelanoma Skin Cancers
ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.
“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.
“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”
Study Design and Results
The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.
The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.
Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.
“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.
Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.
For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.
A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).
Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.
The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.
Limitations and Questions
The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.
Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”
The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.”
Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article first appeared on Medscape.com.
ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.
“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.
“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”
Study Design and Results
The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.
The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.
Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.
“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.
Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.
For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.
A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).
Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.
The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.
Limitations and Questions
The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.
Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”
The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.”
Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article first appeared on Medscape.com.
ORLANDO, Fla. — A study of automated three-dimensional total-body photography (3D TBP) found that it improved “hit” rates of positive malignant biopsies and reduced unnecessary biopsies of skin lesions but left unanswered questions about the practicality of its widespread use and cost-effectiveness.
“We did observe improved biopsy practices and outcomes,” said Jordan Phillipps, MD, a dermatology resident at Mayo Clinic in Jacksonville, Florida, who reported the results of the study during a late-breaker session at the American Academy of Dermatology (AAD) 2025 Annual Meeting.
“We observed reduced unnecessary biopsies, which was driven by benign and premalignant, particularly actinic keratosis, lesions,” Phillipps said. “We observed improved malignancy detection, which was profoundly driven by nonmelanoma skin cancers.”
Study Design and Results
The retrospective study included 410 adult patients who had at least two sessions with the Vectra WB360 3D TBP imaging system at a dedicated 3D imaging clinic at Mayo Clinic in Rochester, Minnesota Patient eligibility for the 3D clinic requires a previous melanoma diagnosis. All study participants also underwent dermoscopy, Phillipps said. Their average age was 51.6 years, and 53% were women.
The study accounted for 5981 total patient encounters, including 1150 dedicated Vectra imaging sessions, Phillipps said. In this group, 3006 biopsies were performed, of which 56% were benign, 32% were malignant, and 12% were premalignant. The study also separately evaluated lesion type, focusing on keratinocytic and pigmented lesions.
Most of the keratinocytic lesions were nonmelanoma skin cancers, he said, whereas the pigmented lesions were mostly benign.
“The intervention did significantly reduce biopsies per encounter by 35%, and this was driven by benign lesions and premalignant lesions, particularly actinic keratosis lesions,” Phillipps said.
Previous studies of automated TBP have been hampered by small study populations, he said, and this is one of the largest studies of the Vectra WB360 device. “Nonmelanoma skin cancers are underreported,” Phillipps said, noting that most studies focus on melanoma and pigmented lesions. “Our aim was to assess the effect of Vectra implementation on biopsy practice and outcomes,” he explained.
For malignant lesions, the investigators observed an improvement in malignancy detection, a modest 1.6% increase in hit rates of positive malignant biopsies, and a modest 1.3% decrease in the number needed to biopsy, he said.
A subgroup analysis of pigmented and keratinocytic lesions demonstrated that improved malignancy detection is “profoundly driven by nonmelanoma skin cancers” of 71% per biopsy, Phillipps said, along with “sizable” increases in the hit rate (+17%) and a reduction in the number of biopsies (–14%).
Melanoma detection decreased by 62% per biopsy. Phillipps said the reduction was probably because of the study methodology, specifically the eligibility requirement of having had a previous melanoma diagnosis. “These patients typically develop only one primary melanoma,” Phillipps said. To test this, the investigators compared melanoma hit rates with a matched, unexposed cohort that did not have Vectra imaging. They found that the hit rates were similar. “So this was reassuring that we weren’t missing any melanomas,” Phillipps said.
The results also showed improved efficacy for detecting severely dysplastic nevi, for which the hit rate increased by 16% and the number needed to biopsy decreased by 13%. “Actinic keratoses lesions were biopsied less,” he said, noting a 50% decrease. Both benign keratinocytic lesions, predominantly seborrheic keratosis and benign lichenoid keratosis, and benign pigmented (benign nevi) lesions were biopsied less.
Limitations and Questions
The highly selective nature of the patient population was a limitation of the study, Phillipps noted, along with financial and logistical challenges that impede the generalizability of the findings. Overall, he said, the study emphasized that 3D TBP is effective in skin cancer screening and diagnosis, notably beyond pigmented lesions.
Kristina Callis Duffin, MD, MS, chair of dermatology at The University of Utah, Salt Lake City, Utah, called the findings “exciting” but noted that the study did not compare results to the gold standard of clinician-performed skin screenings. “That absolutely would be the important way to do it, through a randomized trial,” she said, “but that’s a hard study to do.”
The cost-effectiveness of total-body imaging also needs to be evaluated, Duffin said. “You really have to look at a number of factors in terms of protection compared to a human gold standard, the rates of biopsies,” she said. “There are a lot of things to unpack; that cost-effectiveness has to be balanced with a more accurate diagnosis and reduction of morbidity with multiple biopsies.”
Phillipps reported no relevant financial relationships. Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.
A version of this article first appeared on Medscape.com.
FROM AAD 2025
How Many Patients in Early Cancer Trials Get Drugs Ultimately Approved by FDA?
TOPLINE:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
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:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
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:
One in six patients in phase 2 cancer trials received treatments that were eventually approved by the Food and Drug Administration (FDA), a new analysis found. This proportion increased to 1 in 5 when considering National Comprehensive Cancer Network (NCCN) off-label recommendations and decreased to about 1 in 11 for approved regimens considered to have a substantial clinical benefit.
METHODOLOGY:
- Patients enroll in phase 2 oncology trials seeking access to promising new treatments, but the risk-benefit assessments and the likelihood of receiving a therapy that ultimately gains FDA approval remain unclear. Previous research suggests that the odds are 1 in 83 patients for those enrolled in a phase 1 cancer trial.
- Researchers randomly selected 400 phase 2 cancer trials initiated between November 2012 and November 2015 (to give enough time for an approval to occur); these trials included more than 25,000 patients across 608 specific treatment cohorts testing 332 drugs.
- The primary endpoint was the proportion of patients enrolled in phase 2 trials who received a treatment regimen that later attained FDA approval — defined as the “therapeutic proportion.”
- A secondary endpoint was determining the therapeutic proportion based on the therapeutic value of drugs. The three benchmarks were FDA approval alone, FDA approval plus NCCN off-label recommendations, and FDA approval for drugs considered to have a substantial clinical benefit, based on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).
TAKEAWAY:
- A total of 4045 patients received a treatment regimen that advanced to FDA approval, corresponding to a therapeutic proportion of 16.2%.
- The therapeutic proportion increased to 19.4% when considering NCCN off-label recommendations and decreased to 9.3% for FDA-approved regimens considered to have a substantial clinical benefit, based on the ESMO-MCBS.
- The proportion of patients who participated in a trial in which the drug-indication pairing went on to phase 3 testing was 32.5%.
- Enrollment in a trial featuring biomarker enrichment, an immunotherapy drug, a large phase 2 cohort, and a nonrandomized, industry-sponsored trial all showed a trend toward a higher therapeutic proportion.
IN PRACTICE:
“By entering a phase 2 trial, a patient has a one in six chance of receiving a treatment that will later be approved for their condition,” the authors wrote. “The proportions described here, when juxtaposed with those estimated previously for phase 1 trials, suggest a striking improvement for a patient’s therapeutic prospects. This suggests that phase 1 trials do a good job at protecting patients downstream from unsafe and ineffective cancer treatments.”
In an editorial accompanying the study, Howard S. Hochster, MD, of the Rutgers Cancer Institute in New Brunswick, New Jersey, suggested that the 16.2% therapeutic proportion reported may be understated. For instance, “if using the criterion of drugs that were FDA approved in any indication and dose, the proportion of patient benefit in these trials rises to 38%, with a 51% benefit rate considering inclusion in NCCN guidelines,” he wrote.
SOURCE:
This study, led by Charlotte Ouimet, MSc, Department of Equity, Ethics and Policy, McGill University School of Population and Global Health, Montréal, Québec, Canada, was published online in Journal of the National Cancer Institute.
LIMITATIONS:
The longitudinal design of this study required using a historical cohort of phase 2 clinical trials, which may not reflect current drug development patterns. This study was underpowered to determine trial characteristics that predicted higher therapeutic proportions. Furthermore, the exclusion of cytotoxic drugs from the analysis resulted in a somewhat restricted view of overall drug development.
DISCLOSURES:
This study was supported by the Canadian Institutes of Health Research. The authors reported having no relevant conflicts of interest.
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.
Open Clinical Trials for Patients With Prostate Cancer
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
The clinical trials listed below are open as of March 10, 2025; have ≥ 1 US Department of Veterans Affairs (VA) medical center (VAMC) or US Department of Defense (DoD) military treatment facility location recruiting patients; and are focused on treatments for chronic obstructive pulmonary disease (COPD). For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.
Actively Recruiting
Patient Decision-making About Precision Oncology in Veterans With Advanced Prostate Cancer
This clinical trial explores and implements methods to improve informed decision making (IDM) regarding precision oncology tests amongst veterans with prostate cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Precision oncology, the use of germline genetic testing and tumor-based molecular assays to inform cancer care, has become an important aspect of evidence-based care for men with advanced prostate cancer. Veterans with metastatic castrate-resistant prostate cancer may not be carrying out IDM due to unmet decisional needs. An informed decision is a choice based on complete and accurate information. The information gained from this study will help researchers develop a decision support intervention (DSI) and implement the intervention. A DSI may serve as a valuable tool to reduce ongoing racial disparities in genetic testing and encourage enrollment to precision oncology trials.
ID: NCT05396872
Sponsor; Investigator; Collaborator: University of California, San Francisco; Daniel Kwon, MD; US Department of Defense VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: San Francisco Veterans Affairs Medical Center, CA
Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer (VA STARPORT)
This is a prospective, open-label, multi-center seamless phase II to phase III randomized clinical trial designed to compare SST with or without PET-directed local therapy in improving the castration-resistant prostate cancer-free survival (CRPC-free survival) for veterans with oligometastatic prostate cancer. Oligometastasis will be defined as 1-10 sites of metastatic disease based on the clinical determination of the LSI which incorporates all imaging, clinical, and pathologic data available.
ID: NCT04787744
Sponsor; Collaborator: VA Office of Research and Development; Abhishek Solanki, MD, MS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 19 locations, including Edwards Hines Jr. VA Hospital, Hines, IL
The Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS) (ProGRESS)
Prostate cancer is the most common non-skin cancer among veterans and the second leading cause of male cancer death. Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment. False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them. However, new genetic testing might help identify which men are at highest risk for prostate cancer. This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies. If this genetic test proves beneficial, it will improve the way that health care providers screen male veterans for prostate cancer.
ID: NCT05926102
Sponsor; Collaborator: VA Office of Research and Development; Jason L. Vassy, MD, MPH VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Boston Healthcare System Jamaica Plain Campus, MA
A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss (SNARE)
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
ID: NCT05593497
Sponsor; Collaborator: VA Office of Research and Development; Ryan P. Kopp, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 5 locations, including VA Portland Health Care System, OR
18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
This is a single-center, prospective, exploratory study. Patients with metastatic castration-resistant prostate cancer (mCRPC) scheduled to undergo Lutetium labelled prostate-specific membrane antigen radioligand therapy (LuPSMA RLT) at the West Los Angeles VA (WLA-VA) will be imaged with a baseline F-18 fluorodeoxyglucose positron emission tomography/computed tomography 18F-FDG PET/CT and a 18F-DCFPyL PET/CT (18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid)positron emission tomography/computed tomography , as per standard of care in our institution. All patients further undergo eventual follow-up prostate-specific membrane antigen positron emission tomography (PSMA PET) after the 2nd, 4th, and 6th LuPSMA RLT cycle. In this prospective study, an18F-Fluciclovine positron emission tomography/computed tomography (Axumin PET/CT) will be additionally obtained at baseline (pre-LuPSMA RLT), and after the 2nd, 4th, 6th LuPSMA RLT cycles. Axumin PET/CT will be acquired within 7 days from the PSMA PET.
This study is open to veterans only.
ID: NCT06706921
Sponsor; Collaborator: VA Greater Los Angeles Healthcare System; Gholam Berenji, MD, Janake Wijesuriya, BS VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: VA Greater Los Angeles Healthcare System, CA
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers (VA-BAT)
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis.
ID: NCT05011383
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (CHOMP)
The primary objective is to assess the activity and efficacy of pembrolizumab, a checkpoint inhibitor, in veterans with metastatic castration-resistant prostate cancer (mCRPC) characterized by either mismatch repair deficiency (dMMR) or biallelic inactivation of CDK12 (CDK12-/-). The secondary objectives involve determining the frequency with which dMMR and CDK12-/- occur in this patient population, as well as the effects of pembrolizumab on various clinical endpoints (time to PSA progression, maximal PSA response, time to initiation of alternative anti-neoplastic therapy, time to radiographic progression, overall survival, and safety and tolerability). Lastly, the study will compare the pre-treatment and at-progression metastatic tumor biopsies to investigate the molecular correlates of resistance and sensitivity to pembrolizumab via RNA-sequencing, exome-sequencing, selected protein analyses, and multiplexed immunofluorescence.
ID: NCT04104893
Sponsor; Investigator; Collaborator: VA Office of Research and Development; Matthew B. Rettig, MD; Merck Sharp & Dohme LLC VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 12 locations, including VA Greater Los Angeles Healthcare System, CA
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (COBRA)
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin, to standard of care therapy for patients who have metastatic castrate resistant prostate cancer. This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1, BRCA1, BRCA2, BRIP1, CHEK1, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L inactivating mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5, IV) every 21 days, first or olaparib taken orally (300 mg), twice daily in 28-day cycles, until intolerance, complete response, or progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Participants then cross over from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression (whichever is first). Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria, and at least three weeks have elapsed since last administration of either carboplatin or olaparib. Throughout the study, safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
ID: NCT04038502
Sponsor; Collaborator: VA Office of Research and Development; Robert B. Montgomery, MD; Ryan Burri, MD; Phoebe Tsao, MD, MSc; Maneesh Jain, MD VA Office of Research and Development; Madalina Macrea, MD, PhD
Location: 17 locations, including VA Puget Sound Health Care System, Seattle, WA
Last Month in Oncology: FDA Cancer News Roundup
Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.
Here’s a deeper look of what happened last month.
New Drugs
1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.
Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.
Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.
2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.
Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.
Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.
New or Expanded Indications
1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.
Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).
2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.
Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.
“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.
Drug Commercialization Halt
Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.
Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.
The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.
Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.
A version of this article first appeared on Medscape.com.
Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.
Here’s a deeper look of what happened last month.
New Drugs
1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.
Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.
Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.
2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.
Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.
Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.
New or Expanded Indications
1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.
Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).
2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.
Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.
“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.
Drug Commercialization Halt
Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.
Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.
The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.
Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.
A version of this article first appeared on Medscape.com.
Last month, the United States Food and Drug Administration (FDA) approved two new drugs and two biosimilars as well as halted commercialization for a hemophilia treatment.
Here’s a deeper look of what happened last month.
New Drugs
1. The FDA has approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.) for adult and pediatric patients 2 years or older with neurofibromatosis type 1 and symptomatic plexiform neurofibromas that are not amenable to complete resection.
Approval for this agent was based on overall response rate findings from a multicenter, single-arm, phase 2b trial. The trial, which enrolled 58 adults and 56 pediatric patients with this rare disease, reported confirmed overall response rates of 41% among adults and 52% among children.
Adverse reactions occurring in at least 25% of adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Mirdametinib can also cause ocular toxicity. Treatment should be withheld, discontinued, or the dosage reduced based on the severity of these adverse reactions, according to the FDA notice.
2. The FDA has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC) to treat adult patients with symptomatic tenosynovial giant cell tumors who will not benefit from surgical resection.
Vimseltinib was approved based on findings from the MOTION trial, which included 123 patients randomly assigned 2:1 to vimseltinib 30 mg twice weekly or to placebo for 24 weeks. At 25 weeks, the objective response rate was 40% in the vimseltinib arm and 0% in the placebo arm. The median duration of response was not reached in the vimseltinib arm. Patients receiving vimseltinib also demonstrated significant improvements in active range of motion, physical functioning, and pain at this time. After another 6 months of follow-up, 58% of responders had a duration of response of 9 months or longer.
Treatment-emergent adverse events in MOTION were largely of grade 1 or 2. The most common adverse reactions, occurring in at least 20% of patients, included increased aspartate aminotransferase, periorbital edema, fatigue, rash, and cholesterol.
New or Expanded Indications
1. The FDA has approved a supplemental Biologics License Application for brentuximab vedotin (Adcetris, Seagen Inc.), in combination with lenalidomide and rituximab, for adults with relapsed or refractory large B-cell lymphoma, after at least two prior lines of therapy, who are ineligible for stem cell transplant or chimeric antigen receptor T-cell therapy. This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma.
Approval was based on the randomized, double-blind, placebo-controlled ECHELON-3 trial, which randomly assigned patients 1:1 to receive lenalidomide and rituximab plus either brentuximab vedotin or placebo until disease progression or unacceptable toxicity. Researchers reported a median overall survival of 13.8 months in the treatment group vs 8.5 months in the placebo group (hazard ratio, 0.63).
2. The FDA has approved the Biologics License Application for Ospomyv and Xbryk (Samsung Bioepis Co.) — biosimilars referencing denosumab (Prolia and Xgeva, respectively) — to treat osteoporosis and cancer-related bone loss.
Ospomyv and Xbryk have been approved for use in all indications of the approved reference drugs. Specifically, Xbryk is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors or multiple myeloma, and Ospomyv is indicated in several populations of patients with osteoporosis at high risk for fracture.
“The FDA approval of Ospomyv and Xbryk marks a key step in improving patient access and alleviating treatment cost for patients with osteoporosis and cancer-related bone loss in the United States,” Byoungin Jung, vice president at Samsung Bioepis, said in the news release.
Drug Commercialization Halt
Pfizer announced last month that it will halt the global development and commercialization of its hemophilia gene therapy fidanacogene elaparvovec (Beqvez). The company cited several reasons for the discontinuation, including low demand from patients and doctors.
Beqvez is a one-time therapy approved in the United States last April to treat adults with moderate to severe hemophilia B, a rare bleeding disorder that affects almost 4 in 100,000 men in the United States.
The significant price tag is one reason hematologists have cited for the low uptake. Another barrier is that “we don’t know the long-term outcomes” associated with the drug, pediatric hematologist Ben Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, told this news organization earlier this year.
Other issues include the prospect of newer treatment advances in the hemophilia space and logistical challenges. “There’s just a lot of logistics to getting an institution ready to provide this type of therapy,” Samelson-Jones added.
A version of this article first appeared on Medscape.com.
Patients With Asthma and COPD At Increased Cancer Risk From Microplastics
Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.
Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues.
In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.
The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls.
In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.
“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.
The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.
However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.
Current and Future Implications
The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.
“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said.
“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.
“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.
More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.
The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.
Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues.
In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.
The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls.
In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.
“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.
The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.
However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.
Current and Future Implications
The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.
“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said.
“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.
“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.
More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.
The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Individuals with asthma and chronic obstructive pulmonary disease (COPD) were more vulnerable than healthy controls to epithelial cell changes caused by microplastics exposure, based on data from a new simulation study.
Microplastic fibers present in the ambient air can be inhaled into the lungs and promote a range of complications including oxidative stress, local injury, and cytotoxicity, but data on the effects of microplastic fibers on individuals with obstructive lung diseases are limited, wrote Magdalena Poplinska-Goryca, MD, of the Medical University of Warsaw, Warsaw, Poland, and colleagues.
In a study published in Scientific Reports, the researchers identified 10 adults aged ≥ 18 years with asthma, eight adults aged ≥ 40 years with COPD, and 11 healthy adult controls. Individuals with more serious conditions such as severe asthma or COPD, unstable or uncontrolled disease, concomitant malignancies, or chronic or acute lung disease were excluded.
The researchers obtained nasal epithelial cells from all participants, and exposed these cells to microplastic fibers created by the researchers in a laboratory setting. Overall, asthmatic and COPD airway epithelial cells showed a different reaction to microplastic fibers stimulation compared to healthy epithelial cells. The most significant response was associated with Th2 inflammation, modulation of stress response, and carcinogenesis. No differences in cytotoxic or minor inflammatory effects on epithelial cells of patients with asthma or COPD were noted compared with healthy controls.
In addition, flow cytometric analysis showed increased CD24+ epithelial cells in asthma patients compared to controls after microplastics exposure.
“Many of the gene candidates selected from RNA-Seq analysis are related to cancer (upregulated in many cancer types according to the literature), and the activation of CD24 on primarily ciliated asthmatic epithelial cells after microplastic stimulation further supports this theory,” the researchers wrote.
The findings were limited by several factors including the use of nasal rather than bronchial epithelial cells, which would have yielded more information, the researchers noted. Also, patients with severe asthma and COPD were excluded, they said, because of the impact of oral steroid and antibiotic use by this patient group on epithelial cell immunology that could bias the results of epithelial response to microplastic fiber exposure.
However, the results suggest that “the structural impairment of the airway epithelium in obstructive diseases enhances the impact of microplastic particles compared to healthy epithelium,” the researchers concluded.
Current and Future Implications
The current study is important in addressing the increasing environmental presence of microplastics and their potential impact on respiratory health, said Seyedmohammad Pourshahid, MD, assistant professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.
“By examining how microplastics interact with airway epithelial cells, particularly in individuals with asthma and COPD, the research aims to elucidate mechanisms that could contribute to disease progression or exacerbation,” he said.
“The study’s findings that microplastics did not induce a strong inflammatory response, unlike other pollutants such as PM2.5, were unexpected; instead, microplastics appeared to influence pathways related to airway remodeling and oxidative stress,” Pourshahid noted. “This suggests that microplastics may affect respiratory health through mechanisms distinct from traditional pollutants,” he said.
“While preliminary, this research highlights the potential role of environmental microplastic exposure in respiratory diseases,” Pourshahid told this news organization. “Clinicians should be aware of emerging environmental factors that could impact patient health, especially in individuals with asthma and COPD. This awareness may inform patient education and advocacy for reducing exposure to airborne microplastics,” he said.
More studies are needed to explore the long-term effects of microplastic exposure on respiratory health, particularly in vulnerable populations, said Pourshahid. Research with in vivo models is necessary to confirm the findings and assess potential clinical implications to confirm these findings and assess potential clinical implications, he said. “Understanding the prevalence and sources of daily microplastic exposure can inform public health strategies to mitigate risks,” he added.
The study was supported by the Jakub Potocki Foundation. Paplińska-Goryca and Pourshahid had no financial conflicts to disclose.
A version of this article first appeared on Medscape.com.
Diet Changes Show Promise in Early Prostate Cancer
A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.
Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.
Growing Evidence on Diet
Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.
Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.
To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.
Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.
The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.
For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).
For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.
Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.
McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.
Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”
The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.
A version of this article first appeared on Medscape.com.
A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.
Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.
Growing Evidence on Diet
Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.
Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.
To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.
Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.
The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.
For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).
For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.
Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.
McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.
Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”
The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.
A version of this article first appeared on Medscape.com.
A diet high in omega-3 and low in omega-6 fatty acids, alongside fish oil supplements, may curb the growth of prostate cancer cells in men with early-stage disease, new data showed.
Among men on active surveillance for prostate cancer, consuming this diet for a year led to a significant decrease in the prostate cancer tissue Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death, according to findings from the phase 2 CAPFISH-3 study presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.
“This data is certainly intriguing and supports studies looking at this further in prostate cancer,” Bradley Alexander McGregor, MD, from Dana-Farber Cancer Institute, Boston, Massachusetts, who wasn’t involved in the study, told this news organization. But, McGregor noted, patients were on the diet for 1 year, and the long-term implications of this diet are not known.
Growing Evidence on Diet
Diets that include fried and processed foods tend to be high in omega 6s, while those that include salmon and tuna are higher in omega 3s.
Research has shown that consuming more omega-3 fatty acids is associated with a lower risk for mortality from prostate cancer, explained study investigator William Aronson, MD, with David Geffen School of Medicine at University of California, Los Angeles (UCLA). Research suggests that ingesting more omega-6 accelerates the growth of human tumors in mice, while raising omega-3 levels lowers it. High omega-3 and low omega-6 are also known to have an inhibitory effect on M2-like macrophages, which are the predominant immune cell type in prostate cancer metastasis.
To investigate the impact of these fatty acids on early-stage prostate cancer, Aronson and colleagues conducted a single-center, phase 2, randomized, open-label study in 100 men with grade 1/2 prostate cancer who elected active surveillance.
Patients were randomly allocated 1:1 to a control group that continued their normal diet (minus fish oil) or to an intervention group that followed a low omega-6/high omega-3 diet, supplemented with fish oil (2.2 g/d), for 1 year.
The primary endpoint was the change in Ki-67 index from baseline to 1 year from same-site biopsies between the groups.
For the primary endpoint, the Ki-67 index decreased in the intervention group by 15% from baseline to 1 year and increased in the control group by 24%. The difference between groups was statistically significant (P = .043).
For the secondary endpoints, the intervention led to a reduction in triglyceride levels and macrophage colony stimulating factor but no change in tumor volume grade group, PSA level, or Decipher 22 gene score.
Aronson said the findings support future phase 3 trials incorporating this intervention among men on active surveillance for prostate cancer.
McGregor said it’s important to note that this was “an aggressive intervention with dietary changes and addition of fish oil and patients need to be highly motivated.” Four men discontinued due to adverse effects — primarily gastrointestinal adverse effects such as diarrhea and nausea — larger sample sizes will be key to better understand the tolerability.
Bottom line, said McGregor, “based on this data alone, it should not be recommended but can be considered for highly motivated patients after discussion of the limitations of available data and side effects.”
The study was funded in part by the National Cancer Institute, the UCLA Health Jonsson Comprehensive Cancer Center, Howard B. Klein, and the Seafood Industry Research Fund. Aronson disclosed relationships with AstraZeneca, Bayer, Blue Earth Diagnostics, Janssen Oncology, and Pfizer/Astellas. McGregor disclosed relationships with Arcus Biosciences, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca, Eisai, Exelixis, Genmab, Gilead Sciences, Loxo/Lilly, Pfizer, and Seattle Genetics/Astellas.
A version of this article first appeared on Medscape.com.
FROM GUCS 2025
Next-Gen Sequencing Tumor Testing Remains Low in Prostate and Urothelial Cancer Cases
This article is a based on a video essay. The transcript has been edited for clarity.
I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”
As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.
This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?
This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.
There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.
The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.
By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.
Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.
I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.
Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.
Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.
These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.
Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This article is a based on a video essay. The transcript has been edited for clarity.
I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”
As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.
This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?
This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.
There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.
The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.
By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.
Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.
I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.
Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.
Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.
These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.
Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This article is a based on a video essay. The transcript has been edited for clarity.
I’d like to discuss what I think is a very interesting analysis that we need to see much more of. It’s perhaps not surprising, but the data, I think, are sobering. The paper was published in JAMA Network Open, entitled, “Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.”
As I think most of the listening audience is aware, we are in the midst of an ongoing — I would argue, accelerating — revolution in our understanding of cancer, its development and treatments, based upon our characterization at the molecular level of individual cancers.
This, of course, is changing the treatment paradigms and the drugs that we might have available in the first-, second-, and third-line settings. The question to be asked is, how are we, at a clinical level, keeping up with all of these changes, like those approved by the US Food and Drug Administration, and new diagnostic testing with a variety of molecular platforms?
This particular analysis looked at that specific question in metastatic prostate cancer and urothelial malignancies, obviously including bladder cancer. With the new approvals — including tumor agnostic testing, very specific testing, and very molecularly based drugs that are approved for particular abnormalities — they looked at the percentages of patients and the potential disparities in terms of the testing that has been performed.
There were 11,927 patients with prostate cancer. There were 6490 patients with advanced urothelial malignancies; the majority of these were male, but there were females included in this group.
The researchers looked at 2015 vs 2022 data. It’s not 2024 data, but it goes all the way to the end of 2022, so, not that long ago. In the metastatic prostate cancer group, 19% of patients had undergone molecular testing or next-generation sequencing in 2015.
By 2022, that number had increased, but only to 27%. Three out of four patients with metastatic prostate cancer had not undergone testing to know whether they were potential candidates for specific therapies. I won’t even get into the question of potential germline abnormalities that might be observed that are relevant for other discussions.
Among patients with urothelial cancer, in 2015, 14% had undergone such testing. By 2022, this number was substantially increased to 46.6%, but still, that’s less than 1 out of 2 patients. More than 50% of patients had not undergone the testing, and yet we have therapy that might be available for these populations based on such testing.
I should add that the population of Black, African American, and Hispanic patients was actually considerably lower, percentage-wise, than the numbers that I’ve quoted.
Clearly, there are explanations. There are socioeconomic explanations and insurance coverage explanations. However, the bottom line is that we have therapies available today, and we’ll have more in the future, that are based on knowledge of this testing.
Based on these data, which most recently included 2022 — we’ll see where we are in 2024 and 2025, and with other types — more than half of patients are not getting the testing to know if this is relevant for them and their care.
These are major questions that need to be addressed. Hopefully, answers will be forthcoming and we will see in the future that these percentages will be much higher for the benefit of our patients.
Dr Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships with GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
Immunotherapy Reduces Skin Cancer Precursors
TOPLINE:
Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.
METHODOLOGY:
- This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
- The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
- More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
- The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.
TAKEAWAY:
- At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
- Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
- KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
- Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.
IN PRACTICE:
“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”
SOURCE:
Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.
LIMITATIONS:
Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.
DISCLOSURES:
This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.
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:
Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.
METHODOLOGY:
- This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
- The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
- More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
- The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.
TAKEAWAY:
- At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
- Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
- KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
- Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.
IN PRACTICE:
“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”
SOURCE:
Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.
LIMITATIONS:
Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.
DISCLOSURES:
This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.
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:
Immune checkpoint inhibitors (ICIs) show promise for field cancerization, based on their ability to reduce actinic keratoses (AKs) in a new study.
METHODOLOGY:
- This prospective cohort study included 23 immunocompetent participants (26.1% women; mean age, 69.7 years) from Australia who received ICIs for any cancer between April 2022 and November 2023.
- The most frequently prescribed ICI regimen was a combination of nivolumab and ipilimumab (34.8%), followed by nivolumab monotherapy (26.1%) and cemiplimab (21.7%) or pembrolizumab (17.4%) monotherapy.
- More than half of the patients received ICI therapy for skin cancer (melanoma, 30.4%; cutaneous squamous cell carcinoma, 26.1%); 34.8% had lung cancer; two had other carcinomas.
- The primary outcome was the number of AKs at 12 months after starting ICI therapy; the secondary outcome was the number of keratinocyte carcinomas (KCs) excised 12 months before and after ICI therapy.
TAKEAWAY:
- At 12 months, one patient had complete resolution from AK, and the mean number of AKs significantly decreased from 47.2 at baseline to 14.3 (P < .001).
- Younger patients (66.7% vs 33.3%; P = .007) and those with a history of blistering sunburn (100% vs 0; P = .005) were more likely to experience ≥ 65% reduction in AK count.
- KC incidence in the year before ICI therapy vs the year after initiation dropped from 42 to 17 cases, respectively, and the number of cutaneous squamous cell carcinomas decreased from 16 to 5.
- Adverse events occurred in 11 participants (47.8%), with maculopapular rash or pruritus the most common.
IN PRACTICE:
“This pilot cohort study highlights the potential association of ICI therapy, originally used in cancer treatment, with significant reduction of clinical AKs,” the authors wrote. These findings, they said, “underscore ICIs’ potential as a novel approach to mitigating field cancerization in high-risk populations.”
SOURCE:
Charlotte Cox, MD, MPhil, MPHTM, BMSt, University of Queensland, Brisbane, Australia, led the study, which was published online in JAMA Dermatology.
LIMITATIONS:
Limitations included interrater reliability issues in AK counting. Not all patients completed the follow-up period, and observations about changes after stopping ICI therapy were limited. Surveillance bias could be present in KC reporting.
DISCLOSURES:
This work was supported by grants from the Metro South Health SERTA project and by the French Society of Dermatology, La Ligue Contre le Cancer, the Collège des Enseignants en Dermatologie de France, and the European Association of Dermatology and Venereology. Cox received personal fees from the University of Queensland scholarship funds during this work. Some authors reported receiving personal fees and support from pharmaceutical and cosmetic companies.
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.
Promise for CAR T-Cell Therapies in Solid Tumors?
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.
Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in blood cancers — with six CAR T-cell products now approved by the Food and Drug Administration (FDA) to treat six hematologic malignancies.
For solid tumors, however, the efficacy of CAR T-cell treatments has been limited and progress “more incremental,” Christian Hinrichs, MD, with Rutgers Cancer Institute in New Brunswick, New Jersey, told this news organization. Currently, there are no CAR T-cell therapies approved in the United States to treat solid tumors.
Why have CAR T-cell therapies been less effective against solid tumors?
Perhaps the biggest hurdle is the ability to identify and selectively target specific molecular structures in cancer cells without causing severe toxicity by injuring healthy cells, Hinrichs and coauthors wrote in a recent JAMA review.
CAR T-cells are made up of “T cells genetically engineered to express a synthetic receptor that recognizes a tumor cell-surface protein,” Hinrichs and colleagues explained. But identifying cell surface antigens that are exclusive to solid tumor cells has been a challenge, which means CAR T-cell therapies end up affecting both tumor and healthy tissues.
“This makes it difficult to target and kill all the tumor cells without causing severe toxicity from injury to healthy cells,” Hinrichs explained.
Other common obstacles include challenges penetrating the dense extracellular matrix of solid tumors and the need to overcome inhibitory cells and molecules in the tumor microenvironment.
Despite the challenges and slow progress, some “promising results” have begun to emerge in the solid tumor, CAR T-cell space, Hinrichs said.
A recent phase 1-2 study, for instance, found that 63% (17 of 27) of pediatric patients with heavily pretreated neuroblastoma achieved an overall response with an investigational CAR T-cell therapy, GD2-CART01.
In a recent phase 1 trial, 38 of 98 patients with gastrointestinal cancers (39%) achieved partial or complete responses after receiving an investigational CAR T-cell treatment directed at Claudin18.2. However, the responses were short overall and could have been related to the chemotherapy given before the CAR T-cell infusion.
Another phase 1 trial found that a GPC3-targeted CAR T-cell therapy led to an objective response rate in half (12 of 24) of heavily treated patients with advanced hepatocellular carcinoma, with a disease control rate of almost 91%.
Outside of CAR-T cell therapies, other cell-based treatments have shown promise against solid tumors, including two T-cell therapies recently approved by the FDA.
Last February, the FDA approved the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) for advanced melanoma. In August, the agency approved the T-cell receptor (TCR) therapy afamitresgene autoleucel for advanced synovial sarcoma.
“Response rates for these cellular therapies are in the 30% range, but already there is clear data that there’s durability for some patients, which is very exciting because previously treated patients really have very few treatment options,” Jennifer Brudno, MD, with the National Cancer Institute and coauthor of the JAMA review, said in a journal podcast.
Several cell-based agents are in early trials to treat a range of solid tumors.
Hinrichs and colleagues previously reported findings from a phase 2 clinical trial of TIL therapy for human papillomavirus (HPV) — associated cancers including cervical, oropharyngeal, and anal cancers. Responses occurred in 5 of 18 patients with cervical cancer and 2 of 11 patients with noncervical cancers. “Two of the patients with cervical cancer had complete responses that are ongoing years after a single infusion of cells,” Hinrichs told this news organization.
Hinrichs was also involved in a phase 1 trial of gene-engineered TCR T-cells targeting HPV E7 for HPV-associated cancers reported tumor responses in 6 of 12 patients, including 4 of 8 with tumors refractory to checkpoint blockade immunotherapy. A phase 2 trial is now open at Rutgers Cancer Institute, as is an early trial testing a new TCR T-cell therapy targeting Kita-Kyushu Lung Cancer Antigen-1 to treat metastatic gastric, lung, breast, and cervical cancers.
Despite the encouraging findings, for CAR T-cell and other cell-based therapies to be successful against solid tumors, “we need to develop more treatments directed against antigens that are expressed by most or all the cells in a tumor but not by critical healthy tissues,” Hinrichs said.
“It may also be important to increase the potency of therapeutic cells and develop more sophisticated methods of antigen targeting that can better distinguish between tumors and healthy tissues,” he noted.
Brudno reported being an unpaid scientific advisory board member for and receiving travel expenses from Kyverna Therapeutics. Hinrichs reported receiving personal fees from Neogene Therapeutics, Capstan Therapeutics, GlaxoSmithKline, Vir Biotechnology, and PACT Pharma; equity from Scarlet TCR (company officer); and sponsored research agreements from T-Cure Biosciences and Neogene Therapeutics outside the submitted work. He also holds several patents related to cellular therapies.
A version of this article first appeared on Medscape.com.