[¹⁷⁷Lu]-PSMA-617 Has Activity in Castration-Resistant Prostate Cancer

Patients with progressive metastatic castration-resistant prostate cancer have limited treatment options, and new therapeutic approaches are needed. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in prostate cancer, and a small molecule labeled to a radioactive beta-emitter, Lutetium-177 [¹⁷⁷Lu]-PSMA-617 (LuPSMA), binds with high affinity to PSMA to allow for delivery of radiation to the tumors while minimizing damage to the surrounding normal tissue. Hofman, Violet, and colleagues evaluated the efficacy and safety of LuPSMA in a prospective phase II trial of 30 patients with metastatic castration-resistant prostate cancer who had progressed after standard therapies including taxane-based chemotherapy and second-generation antiandrogens (abiraterone or enzalutamide). The primary endpoints included PSA response, defined as a greater than 50% PSA decline from baseline, toxicity, and radiologic response. A PSA decline of 50% or more occurred in 17 of 30 (57%) patients. The median PSA progression-free survival was 7.6 months and median overall survival was 13.5 months. Of the 17 patients with evaluable nodal or visceral lesions at baseline, 14 (82%) experienced objective responses, including 5 complete and 9 partial responses. LuPSMA was well tolerated with predominantly grade 1 treatment-related toxicities. Further, LuPSMA treatment produced clinically meaningful improvements in pain severity and interference scores, and 37% of patients experienced a ten point or more improvement in global health score by the second cycle of treatment. Taken together, these findings indicate that radionuclide treatment with LuPSMA is well tolerated and achieves a high response rate in men with castration-resistant prostate cancer who have progressed after conventional therapies. Based on these findings a randomized clinical trial is under way comparing LuPSMA with cabazitaxel chemotherapy in men with prostate cancer.

Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [¹⁷⁷Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018 May 8 [Epub ahead of print].

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