Advanced Prostate Cancer: PSMA-Targeted Radioligand Therapies - Episode 5

The VISION Study of 177Lu-PSMA-617 in mCRPC

Results of the phase 3 VISION study of 177Lu-PSMA PET in advanced prostate cancer are described.

Neal Shore, MD: The phase 3 VISION trial that was very nicely presented by Dr Mike Morris at ASCO [American Society of Clinical Oncology Annual Meeting] this year, was a landmark study. We were very fortunate to be a urology site, and I believe there was no other urology community-based site that accrued more patients than we did. I had a really fortunate opportunity to be part of that study. This study involved patients who had mCRPC [metastatic castration-resistant prostate cancer], who had progressed on at least 1 novel hormonal agent, and at least a taxane-based therapy. Many of these patients had had multiple taxane therapies and multiple novel hormonal agents. These patients had high tumor burden. They had progressed on numerous lines of therapy yet were highly motivated to be randomized to receive lutetium-177-PSMA [prostate-specific membrane antigen]–617 PET [positron emission tomography].

Because lutetium is the active payload, as well as randomized to, in an open-label fashion, so it’s the best standard of care. This may have included steroid supplementation, additional androgen receptor antagonists, and other aspects of good standard of care. Fortunately, this was a remarkably positive trial both from an overall survival and hazard ratio standpoint. Therapy is administered in a multidisciplinary fashion with urologists, medical oncologists, nuclear medicine radiologists, and radiation oncologists. Primarily, it’s important that whoever is administering the intravenous therapy is giving it with appropriate licensure. Typically, that’s reviewed for appropriate handling of the material—at least in the United States—on a state-by-state basis by the Nuclear Regulatory Commission.

Overall, as has been shown in other phase 1 and 2 studies, lutetium PSMA is very well tolerated. One needs to monitor for some potential myelosuppression. There can be some issues regarding dysgeusia or taste loss, or dryness within the mouth, but these are typically of a low-grade nature. The VISION trial wonderfully demonstrated the benefit of delaying disease progression by rPFS [radiographic progression-free survival] monitoring, as well as hazard ratio and a survival benefit of approximately 0.6, which is important because its unique mechanism of action supplements the already approved unique mechanisms of action of ARPI [androgen receptor pathway inhibition] drugs, taxanes, other radiopharmaceuticals such as Radium 223, and even immunotherapeutics. This is extremely important. This study will clearly lead to additional trials, looking in the prechemotherapy mCRPC and mCSPC [metastatic castration-sensitive prostate cancer] populations. Assuredly, there will be other radioisotopes that can be linked to antibodies that will add to the opportunities for trials, research, and therapeutic awareness throughout the prostate cancer journey.