Invited discussant of the VISION trial, Mary-Ellen Taplin, MD, of Dana-Farber Cancer Institute, Boston, commented on the study, noting that she was a co-investigator of the trial.
“Patients with metastatic castration-resistant prostate cancer have a number of treatment options. There are 10 approved treatments in addition to standard androgen-deprivation therapy. Unfortunately, the duration of response with these agents is often short. If lutetium-177–PSMA-617 (LuPSMA) is approved, the label would be for late-stage metastatic castration-resistant prostate cancer,” she told listeners. “There has been much promise and enthusiasm that PSMA [prostate-specific membrane antigen] can be targeted for diagnosis with PSMA PET and as a therapeutic, in this instance with radioactive lutetium.”
“The high rate of PSMA positivity of those enrolled in the study begs the question of whether such strict PSMA criteria are needed. It’s not clear whether the study would have been positive in a nonselected population,” Dr. Taplin noted.
In addition, Dr. Taplin was disappointed in the low enrollment of minorities in the trial: 6.6% were Black and 2.4% were Asian. “Prostate cancer is more common and lethal in Black individuals. Currently, my institution is making a significant commitment to improve resources for access to trials,” she noted. Dr. Morris agreed that efforts should be made to increase minority enrollment in clinical trials for prostate cancer.
Thoughts on Survival Outcomes
“The results for radiographic progression-free survival are very positive. The curves remain apart, with an almost 38% reduction in the risk of disease progression or death,” stated Dr. Taplin.
“However, I am disappointed by the overall survival results. Based on 30 years of trials that prolong overall survival by 2 to 4 months, I had hoped for more [with LuPSMA],” Dr. Taplin commented. “Looking at the survival gains in trials in metastatic castration-resistant prostate cancer, we can conclude that the efficacy in this trial was no better or worse than other approved agents. Of notable value, however, is this mechanism of action differs from that of hormone therapy, and this radioligand may be used sequentially.”
Regarding the rate of radiographic progression-free survival in the trial, Dr. Taplin said: “Radiographic progression-free survival improved by 5.6 months in patients treated with the radioligand. It is noteworthy that radium-223 did not improve progression-free survival in the trials. I cannot understate the importance to patients of not experiencing disease progression. When we discuss this new therapy with patients, we need to alert them to the potential side effects of fatigue, dry mouth, nausea, and possibly vomiting, as well as myelosuppression. We can all agree this will be a valuable treatment option for patients. It is already being used in Germany and in other countries in Europe.”
“If LuPSMA is approved by the [U.S. Food and Drug Administration], we will have an addition to our armamentarium of palliative systemic radiopharmaceuticals. I have confidence that, in the future, radiopharmaceuticals will be even more impactful,” Dr. Taplin predicted. More than 30 new radiopharmaceuticals are being developed in various cancers, she added.
DISCLOSURE: Dr. Taplin has received honoraria from AbbVie, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, Bayer, Celgene, Clovis Oncology, Constellation Pharmaceuticals, GSK, Guidepoint Global, Incyte, Janssen-Ortho, Merck, Myovant, Pfizer, Progenics, Research to Practice, Roivant Sciences, and UpToDate; has served as a consultant or advisor to AstraZeneca, Bayer, Best Doctors Inc, Clovis Oncology, Guidepoint Global, Incyte, Janssen-Ortho, Myovant Sciences, Pfizer, Research to Practice, and UpToDate; has an immediate family member who has served as a consultant or advisor to Arcus; has received institutional research funding from Bayer, Janssen-Ortho, Medivation, and Pfizer; has been reimbursed for travel, accommodations, or other expenses by Astellas Pharma, Bayer, Clovis Oncology, Incyte, Janssen Oncology, Medivation, Pfizer, and Tokai Pharmaceuticals.
Lutetium-177–PSMA-617 (LuPSMA)—an investigational radiolabeled small molecule—significantly improved radiographic progression-free survival and overall survival when added to the standard of care compared with the standard of care alone for men with metastatic castration-resistant prostate cancer...