Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as an initial treatment in unselected patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the China cohort of the phase 3 TALAPRO-2 trial.

5047 Background: In the China cohort of the TALAPRO-2 study, unselected pts with mCRPC who received TALA + ENZA had improved radiographic progression-free survival per BICR (rPFS; HR=0.30; 95% CI, 0.17–0.56; P <0.0001; data cutoff: Nov 15, 2023), consistent with the global population (HR=0.63; 95% CI, 0.51–0.78; P <0.0001; data cutoff: Aug 16, 2022). In final prespecified analyses, TALA + ENZA significantly improved OS vs PBO + ENZA in the global population. Here we report final OS, a descriptive update of rPFS, and an extended follow-up of secondary outcomes in the China cohort. Methods: The China cohort includes pts from the unselected cohort 1 of TALAPRO-2 and China extension (unselected homologous recombination repair [HRR] gene status). Pts had asymptomatic/mildly symptomatic mCRPC, received ongoing androgen deprivation therapy, and were prospectively tested for HRR alterations in tumor tissue. Pts were randomized 1:1 to TALA 0.5 mg/day (moderate renal impairment 0.35 mg/day) or placebo (PBO); all pts received ENZA 160 mg/day. Primary endpoint was rPFS by BICR. OS was a key secondary endpoint. Other secondary endpoints included BICR-assessed objective response rate (ORR), time to prostate-specific antigen (PSA) progression, safety, and pt-reported outcomes. All reported P values are 2-sided. Results: Overall, 125 pts were randomized (TALA + ENZA, 63; PBO + ENZA, 62). At data cutoff (Sep 3, 2024; median follow-up, 33.2 mo in both arms) 35 pts (56%) in the TALA + ENZA arm and 41 pts (66%) in the PBO + ENZA arm had died. Clinically meaningful benefit in OS with TALA + ENZA vs PBO + ENZA was observed: HR=0.591 (95% CI, 0.369–0.944; P =0.0262); median OS (95% CI), 36.9 mo (21.7–42.4) vs 24.1 mo (16.8–30.5), respectively. Updated rPFS by BICR continued to favor TALA + ENZA vs PBO + ENZA (HR=0.312; 95% CI, 0.173–0.561; P <0.0001, median rPFS, 33.3 vs 10.5 mo, respectively). TALA + ENZA was favored vs PBO + ENZA in ORR by BICR (50% vs 32%, respectively; P =0.2845) and time to PSA progression (HR=0.540; 95% CI, 0.298–0.976; P =0.0411). Consistent with global and China cohort primary results, the most common grade ≥3 treatment-emergent adverse events (TEAEs) with TALA + ENZA were anemia (57%) and neutropenia (32%). TEAEs were generally manageable; 14 pts (22%) discontinued TALA due to TEAEs. No clinically meaningful between-arm differences were observed in global health status/quality of life (QoL) measured by EORTC QLQ-C30, except for role functioning, which favored TALA + ENZA. Conclusions: At extended follow-up, initial treatment with TALA + ENZA resulted in clinically meaningful improvement in OS, rPFS by BICR, and secondary efficacy endpoints vs PBO + ENZA in unselected pts with mCRPC in the TALAPRO-2 China cohort. No new safety signals were identified; QoL was maintained. Clinical trial information: NCT03395197 .