1807P Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Subgroup analyses of the all-comers cohort from TALAPRO-2 by homologous recombination repair (HRR) status

The randomized, Phase 3, placebo (PBO)-controlled TALAPRO-2 study demonstrated statistically significant improvements in radiographic progression-free survival (rPFS) for 1st-line TALA + ENZA vs PBO + ENZA in patients (pts) with mCRPC in all-comers and in HRR subgroups (HRR-deficient [HRR+] and HRR-non-deficient [HRR-] or unknown). Here, we report baseline characteristics and secondary efficacy and safety endpoints for all-comers by HRR status. Pts randomized 1:1 to TALA 0.5 mg or PBO, + ENZA 160 mg/day, were stratified by prior abiraterone or docetaxel for castration-sensitive PC (yes vs no) and by HRR status (HRR+ vs HRR-/unknown). The primary endpoint was rPFS by BICR per RECIST 1.1/PCWG3. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to PSA progression, time to initiation of cytotoxic chemotherapy, time to progression on first subsequent antineoplastic therapy or death (PFS2), and safety. Of 805 enrolled pts, all had prospective tumor tissue HRR test results. Overall, baseline characteristics were relatively well-balanced between treatment groups and by HRR status; however, in the younger group (age <65 y), there were more HRR+ (29.6%) than HRR-/unknown (19.3%) pts, and HRR+ pts had evidence of more aggressive disease (Table). Treatment with TALA + ENZA improved ORR, and prolonged time to PSA progression; time to initiation of cytotoxic chemotherapy; and PFS2 vs PBO + ENZA, with benefit seen in both HRR+ and HRR-/unknown subgroups (Table). OS remains immature. Further data will be presented on baseline characteristics, efficacy, and TEAEs by treatment group for HRR+ and HRR-/unknown subgroups. Table: 1807PHRR+HRR+HRR-/unknownHRR-/unknownTALA + ENZA (N=85)PBO + ENZA (N=84)TALA + ENZA (N=317)PBO + ENZA (N=319)Gleason score ≥8N (%)69 (81.2)65 (77.4)212 (66.9)218 (68.3)Time since initial diagnosisMedian, mo24.326.033.141.0ORRN332687106% (95% CI)78.8 (61.1–91.0)46.2 (26.6–66.6)55.2 (44.1–65.9)43.4 (33.8–53.4)P0.0100.10Time to PSA progressionN3842126135Median, mo26.711.126.619.2HR (95% CI)0.53 (0.34–0.82)0.78 (0.62-1.00)P0.00400.050Time to cytotoxic chemotherapyN242459115Median, moNRNRNRNRHR (95% CI)0.71 (0.40–1.26)0.44 (0.32–0.61)P0.24<0.0001PFS2N2134105109Median, mo36.430.8NR35.3HR (95% CI)0.47 (0.27–0.81)0.88 (0.67–1.14)P0.00590.33P values 2-sided Open table in a new tab P values 2-sided TALA + ENZA demonstrated improvements in secondary efficacy endpoints over PBO + ENZA as 1st-line treatment in pts with mCRPC in both HRR+ and HRR-/unknown subgroups.