Multicenter randomized phase 2 trial of enzalutamide with or without [¹⁷⁷Lu]Lu-PSMA-617 for mCRPC: overall survival and quality of life

The phase 2 ENZA-p trial, at 15 centers in Australia, randomized patients with PSMA PET-CT positive high-risk metastatic castration-resistant prostate cancer (mCRPC) to first-line enzalutamide with or without [¹⁷⁷Lu]Lu-PSMA-617. Overall survival and health-related quality of life results of the trial have now been published. Median OS was 34 months in the Lu-PSMA-617 plus enzalutamide group versus 26 months in the enzalutamide alone group (HR 0.55; p=0.0053). Deterioration-free survival was better in the Lu-PSMA-617 plus enzalutamide group than in the enzalutamide alone group for both physical function and overall health; main scores for pain and fatigue were better in the Lu-PSMA-617 plus enzalutamide group than in the enzalutamide alone group, while the opposite was seen for xerostomia. Grade 3 and 4 treatment-related adverse events were seen in 46% of patients in the Lu-PSMA-617 group plus enzalutamide group and 44% in the enzalutamide alone group; there were no grade 5 TRAEs. The authors conclude that the addition of [¹⁷⁷Lu]Lu-PSMA-617 to first-line enzalutamide was associated with improved overall survival and some aspects of HRQOL among patients with high-risk mCRPC.