Combining ARPIs With Radionuclide Therapy Tied to Better Survival in Metastatic CRPC

A secondary analysisopens in a new tab or window of the phase III VISION trial presented at this year’s American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposiumopens in a new tab or window found that adding androgen receptor pathway inhibitors (ARPIs) to ¹⁷⁷Lu-PSMA-617 (LuPSMA; Pluvicto) was associated with a 5.5-month overall survival (OS) benefit for patients with metastatic castration-resistant prostate cancer (mCRPC).

In this exclusive MedPage Today video, Omid Yazdanpanah, MD, of the University of California Irvine, discusses the findings and their implications for clinical practice.

Following is a transcript of his remarks:

The VISION trialopens in a new tab or window was a phase III trial, multi-national, evaluating the efficacy and safety of LuPSMA with standard care versus standard care alone in the treatment of metastatic castration-resistant prostate cancer.

For that trial, the eligible patients were the ones who had metastatic castration-resistant prostate cancer with at least one prior ARPI, an androgen receptor pathway inhibitor, and one or two taxane-based chemotherapies. And they found that there was an improved PFS and OS for the patients who received LuPSMA, which led to the FDA approvalopens in a new tab or window for treatment of patients with metastatic castration-resistant prostate cancer.

But in this secondary analysis, we specifically focus on the patients who only received LuPSMA, and our key question was [what was] the efficacy and safety of concurrent ARPIs with LuPSMA for treatment of these patients?

So we had two arms, the ones who had LuPSMA with concurrent ARPI versus the arm for the patients who received LuPSMA without concurrent ARPIs.

So we retrospectively analyzed the efficacy and safety profile. First of all, speaking of the patient characteristics, the trial was not designed to look at these specific questions. Although most of the characteristics were balanced between the two arms, including median age, advanced Gleason score 8 to 10, and metastatic site distribution, there were some imbalances, like PSA [prostate-specific antigen] level, LDH [lactate dehydrogenase] level, and more prior taxane-based chemotherapy in the patients who did not receive an ARPI.

Taking that into consideration, there was a 5.5-month OS benefit for the patients who received concurrent ARPIs, 17.8 months for the patients who received concurrent ARPI with LuPSMA versus 12.4 months for the patients who did not receive ARPI with LuPSMA. However, the PSA progression-free survival and radiographic progression-free survival was not statistically significant. Both of these endpoints were trending toward better outcomes with concurrent ARPIs. PSA PFS was 8.6 months versus 7.3 months. And for radiographic PFS, it was 10.2 months versus 8.5 months.

The overall adverse event rates were similar between the two groups. Death due to adverse events was reported in eight patients, 2.8% of patients with concurrent use of ARPIs and 4.5% in patients without concurrent ARPIs.

Our study findings actually were aligned with the ENZA-p studyopens in a new tab or window that was presented at ASCO GU, which showed that the combination of enzalutamide and LuPSMA led to improvement of PSA and radiographic progression-free survival and improved overall survival at around 8 months.

However, because of the confounders in our study and retrospective nature of the analysis, this study was determined to be thought-provoking and hypothesis-generating for future trials. We’ll be conducting randomized trials to evaluate the efficacy and safety of concurrent ARPI with LuPSMA for treatment of metastatic castration-resistant prostate cancer to evaluate the findings that we had in this secondary analysis.