Multinational phase 3 trial of ¹⁷⁷Lu-PSMA-617 for PSMA-positive metastatic APMN/S prostate cancer

A standard of care for patients with metastatic androgen pathway modulator naïve/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is ADT plus ARPI until progression. The phase 3 PSMAddition trial (at 169 sites across 20 countries) evaluated adding ¹⁷⁷Lu-PSMA-617 to ADT plus ARPI for PSMA-positive metastatic APMN/S prostate cancer. Patients were randomized 1:1 to ¹⁷⁷Lu-PSMA-617 (every 6 weeks for up to six cycles) plus ADT plus ARPI (¹⁷⁷Lu-PSMA-617 arm; n=572) or ADT plus ARPI (control arm; n=572). The primary endpoint was centrally assessed radiographic progression-free survival (rPFS). At a median rPFS follow-up of 19.6 months (IQR 14.0-24.1), radiographic disease progression or death had occurred in 24% of the patients in the ¹⁷⁷Lu-PSMA-617 arm and 30% of patients in the control arm. rPFS was significantly improved by addition of ¹⁷⁷Lu-PSMA-617 to ADT plus ARPI (HR 0.72; p=0.0021; median rPFS not reached in either arm). Grade 3 or worse adverse events occurred in 51% (¹⁷⁷Lu-PSMA-617 arm) versus 43% (control arm); serious adverse events occurred in 32% versus 29%. The authors conclude that combining ¹⁷⁷Lu-PSMA-617 with ADT plus ARPI prolonged rPFS in patients with PSMA-positive metastatic APMN/S prostate cancer, without unexpected safety findings.