Publication: American Urological Association Annual Meeting Plenary, May 3, 2024
Dana-Farber Cancer Institute author: Xiao X. Wei, MD
Summary: In a follow-on analysis of results from the phase 3 PSMAfore study, clinical investigators from Dana-Farber and elsewhere found that clinical outcomes consistently favored 177Lu-PSMA-617 over a change from one androgen receptor pathway inhibitor (ARPI) to another, regardless of which ARPI patients received first. The trial enrolled 468 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had progressed after one prior ARPI treatment and had never received taxane chemotherapy for metastatic disease. Patients who enrolled in the trial were assigned to either a change in ARPI, for example from abiraterone to enzalutamide or vice versa, or 177Lu-PSMA-617, a prostate-specific antigen (PSMA)-targeted radioligand therapy. This analysis found that treatment with 177Lu-PSMA-617 prolonged radiographic progression-free survival, improved PSA response rate, and increased objective response rate compared to a change in ARPI, regardless of whether patients had received prior abiraterone or enzalutamide. Those treated with 177Lu-PSMA-617 after abiraterone fared better than those previously treated with enzalutamide, though all results consistently favored 177Lu-PSMA-617 over a change to a different ARPI.
Significance: The approval of 177Lu-PSMA-617 for patients with mCRPC post-ARPI and post-taxane chemotherapy in March of 2022 based on the VISION clinical trial was a paradigm shift for the management of advanced prostate cancer. The PSMAfore clinical trial was designed to determine if 177Lu-PSMA-617 could also benefit a broader group of patients with mCRPC who have progressed on ARPI but have not received taxane chemotherapy. This data, along with the overall study results, support the consideration of 177Lu-PSMA-617 as a new standard treatment approach for this prevalent population of patients with mCRPC.
Funding: Novartis
