Multinational phase 3 trial of PARP and androgen-signaling inhibition plus ADT in metastatic prostate cancer

A previous trial involving patients with metastatic prostate cancer that was resitant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes. The multinational phase 3 TALAPRO-3 trial randomized patients with metastatic androgen pathway modulation-sensitive (APMS) prostate cancer harboring alterations in homologous recombination repair genes 1:1 to receive talazoparib plus enzalutamide (talazoparib group; n=300) or placebo plus enzalutamide (control group; n=299). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (versus non-BRCA) mutation status. The primary endpoint was investigator-assessed imaging-based progression-free survival. At 3 years, the progression-free survival rate was 77% in the talazoparib group and 56% in the control group (HR 0.48; p<0.001). In this interim analysis, overall survival at 3 years was 78% in the talazoparib group and 72% in the control group (HR 0.77; 95% CI 0.56-1.04). Serious adverse events were reported in 42% and 32% of patients in the talazoparib group and the control group, respectively. Two treatment-related deaths occurred in the talazoparib group. The authors conclude that addition of talazoparib to enzalutamide led to significantly better imaging-based progression-free survival among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide.