Discussant Scott T. Tagawa, MD, MS, of Weill Cornell Medicine, New York, congratulated Dr. Hofman and coauthors on this first randomized trial of any PSMA-targeted therapy and was cautiously optimistic about the targeted radioligand treatment being adopted as post-docetaxel therapy in men with metastatic castration-resistant prostate cancer.
Regarding the study design, Dr. Tagawa said that due to the use of stricter PSMA and FDG-imaging screening than in the past, 28% of screened patients were not eligible, as opposed to approximately 10% in other prospective studies utilizing PSMA PET alone.
Scott T. Tagawa, MD, MS
“There are no data to suggest that targeting PSMA leads to decreased expression of PSA, so PSA response as a comparative endpoint is fair. In this open-label, nonblinded trial, many more men withdrew from treatment in the cabazitaxel arm, yet the primary endpoint remained statistically significant on sensitivity analysis favoring LuPSMA,” Dr. Tagawa commented. Regarding efficacy, “we await radiographic progression-free survival, overall survival, patient-reported outcomes on quality of life, and other results,” he said.
No new toxicities were identified in the trial. Febrile neutropenia was reported in 8% of the cabazitaxel-treated patients and 0% in the LuPSMA arm. “However, xerostomia in patients receiving LuPSMA deserves further discussion, as grade 2 xerostomia can be clinically meaningful. Fortunately, 75% of cases were grade 1,” he continued.
“Does Lu-177–PSMA-617 represent a new standard of care? In isolation, it is too early to say yes. Fortunately, the results of the VISION study will add to the body of evidence and, if results are positive, will hopefully lead to wide availability of the drug,” he concluded.
DISCLOSURE: Dr. Tagawa has served as a consultant for Sanofi, Medivation/Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, AbbVie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, Advanced Accelerator Applications/Novartis, Genomic Health, Point Pharma, and Ambrx; and has received institutional research funding from Sanofi, Medivation/Astellas, Dendreon, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, Bristol Myers Squibb, Inovio, AstraZeneca, Immunomedics, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, AbbVie, Karyopharm, Seattle Genetics, and Advanced Accelerator Applications/Novartis.
Initial results of the randomized phase II TheraP trial showed that therapy directed to prostate-specific membrane antigen (PSMA) with lutetium-177–labeled PSMA-617 (LuPSMA) significantly improved prostate-specific antigen (PSA) response compared with cabazitaxel in men with metastatic...