Abstract
BACKGROUND: In TALAPRO-2, the poly(ADP-ribose) polymerase inhibitor talazoparib plus the androgen receptor-signaling inhibitor enzalutamide improved radiographic progression-free survival (rPFS) versus placebo plus enzalutamide (hazard ratio [HR] = 0.63; 95% CI, 0.51-0.78) in molecularly unselected patients with metastatic castration-resistant prostate cancer (mCRPC). We report an exploratory analysis of efficacy, safety, and pharmacokinetics in Japanese patients enrolled in the TALAPRO-2 study. METHODS: The ongoing, multinational, randomized, double-blind, phase 3 TALAPRO-2 study enrolled patients with mCRPC receiving ongoing androgen deprivation therapy. Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations and randomized 1:1 to receive talazoparib or placebo plus enzalutamide once daily. The primary endpoint was rPFS by blinded independent central review (BICR). Secondary endpoints included overall survival, objective response, safety, and pharmacokinetics. RESULTS: For the 116 Japanese all-comers patients enrolled in TALAPRO-2, the HR for rPFS was 0.89 (95% CI, 0.45-1.75) for the talazoparib versus placebo arm; among those with HRR-deficient disease, the HR was 0.58 (95% CI, 0.16-2.20). Among patients with BRCA1/2 gene alterations in the HRR-deficient population (n = 10), the HR for rPFS was < 0.01 (95% CI, < 0.01-not reached) for the talazoparib versus placebo arm. In the all-comers population, the objective response rate by BICR was 55% (all complete responses) in the talazoparib arm versus 36% in the placebo arm. The safety profile of talazoparib plus enzalutamide was similar between Japanese patients and the overall all-comers population; no new safety signals were identified. Anemia was the most common grade 3/4 treatment-emergent adverse event (55%) and cause of talazoparib discontinuation (12%). Talazoparib C(trough) was comparable across Japanese, Asian, and non-Asian subgroups. CONCLUSIONS: In this exploratory analysis, efficacy outcomes with talazoparib plus enzalutamide in Japanese patients in TALAPRO-2 were consistent with those in the overall all-comers population. The safety profile and pharmacokinetics of the combination were similar between Japanese patients and the overall all-comers population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03395197.