Radioligand Therapy 177Lu-PSMA-617 in Progressive PSMA-positive mCRPC - Episode 2

Response to LuPSMA Therapy in mCRPC

Andrew J. Armstrong, MD, MSc, discusses the survival benefit of LuPSMA therapy in patients with metastatic castration-resistant prostate cancer and evaluates the response to therapy compared with other agents.

Andrew J. Armstrong, MD, MSc: Michael Morris, MD, while presenting the VISION trial at ASCO [American Society of Clinical Oncology] conference, mostly covered the outcomes according to overall and progression-free survival according to subgroups based on age, based on prior AR [androgen receptor] therapies, as compared to LDH [lactate dehydrogenase] levels, liver metastases, functional status, and race. There was no clear heterogeneity in outcomes based on those factors for progression-free survival. There were benefits to the approach of the VISION trial in basically all of the subgroups that were identified and explored in this ASCO abstract. For overall survival, however, what I would say is that while almost all the subgroups benefitted, the patients with liver metastases seemed to have a diminished survival benefit. This was based on a small subgroup of patients. Only about 80 patients had liver metastases, so take that with a big grain of salt. But again, like I said, patients with liver metastases tend to be enriched in PSMA [prostate-​specific membrane antigen]-negative disease. All the other subgroups tended to have a survival benefit.

The main comparison that I look at for this VISION trial, in this more third-line setting, would be the PSMA lutetium against cabazitaxel, or PSMA lutetium against radium 223. Both agents are FDA [Food and Drug Administration]-approved. Both are life-prolonging. Both improve survival by about 20% to 30% for this patient population. However, radium is really selective, and it is only for patients that have a bone-predominant pattern of spread. It would not be appropriate for patients with bulky soft tissue disease or visceral metastases. That is where PSMA lutetium and cabazitaxel are more active. Now, cabazitaxel is an active agent. In a randomized trial, called the CARD trial, cabazitaxel did improve progression-free and overall survival as compared to a second AR inhibitor. That was published in the New England Journal [of Medicine]. We do not have a formal phase 3 comparison of PSMA lutetium against cabazitaxel. We have smaller randomized trials, where the progression-free survival was nearly identical between these 2 approaches. However, the toxicities differed. The PSA [prostate-specific antigen] responses did differ, and they favored more PSMA lutetium. There was lower toxicity, so there were probably better quality of life and better PSA outcomes.

Transcript edited for clarity.