Subject terms
TALAPRO-2, tumor, mCRPC, prostate cancer
TUMOR, METASTATIC CASTRATION-RESISTANT PROSTATE CANCER, PROSTATE CANCER, DNA DAMAGE
Preclinical evidence has suggested 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 their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; In the homologous recombination repair-deficient population of TALAPRO-2, a placebo-controlled phase 3 trial, treatment of patients with metastatic castration-resistant prostate cancer with the poly(ADP-ribose) polymerase inhibitor talazoparib plus enzalutamide led to prolonged progression-free survival compared with placebo plus enzalutamide.