Multinational phase 3 trial of first-line talazoparib with enzalutamide for HRR-deficient metastatic castration-resistant prostate cancer

Preclinical evidence suggests an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for co-inhibition of AR and PARP for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The multinational phase 3 TALAPRO-2 trial randomized HRR-deficient mCRPC patients to first-line talazoparib plus enzalutamide (n=200) or placebo plus enzalutamide (n=199). The primary endpoint was radiographic progression-free survival. The figure shows that rPFS was not reached after 40 months of follow-up in the talazoparib plus enzalutamide group and was 13.8 months in the placebo plus enzalutamide group (HR 0.45; p<0.0001). Data for overall survival are not yet mature but also favor talazoparib plus enzalutamide over placebo plus enzalutamide (not reached versus 33.7 months; HR 0.69; p=0.07). Common adverse events in the talazoparib plus enzalutamide group were anemia, fatigue, and neutropenia. The authors conclude that among patients with mCRPC harboring HRR gene alterations, addition of talazoparib to first-line enzalutamide was associated with significantly improved rPFS.