Randomized phase 2 trial of lutetium-177-PSMA-617 plus enzalutamide versus enzalutamide alone for metastatic castration-resistant prostate cancer

Enzalutamide and lutetium-177 (¹⁷⁷Lu)-PSMA-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. The multicenter ranomized phase 2 ENZA-p trial in Australia compared ¹⁷⁷Lu-PSMA plus enzalutamide versus enzalutamide alone as first-line treatment for mCRPC patients with risk factors for early progression on enzalutamide. The median PSA progression-free survival was 13.0 months in the combination group versus 7.8 months in the enzalutamide alone group. Grade 3 or higher adverse events occurred in 40% of patients in the combination group and in 41% of patients in the enzalutamide alone group. The authors conclude that addition of ¹⁷⁷Lu-PSMA to first-line enzalutamide improved PSA progression-free survival among mCRPC patients with risk factors for early progression on enzalutamide.