Metastatic prostate cancer research: PSMAfore follow-on study favors radioligand therapy over change to androgen receptor pathway inhibition

Study Title: Efficacy of [177Lu]Lu-PSMA-617 versus ARPI change in taxane-naive patients with metastatic castration-resistant prostate cancer by pre-randomization ARPI (PSMAfore)

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

Contact:  Victoria Warren, 617-939-5531, victoria_warren@dfci.harvard.edu