Final patient-reported outcomes (PROs) in men with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations receiving initial treatment with talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA in the TALAPRO-2 study.

Abstract

11121 Background: The phase 3 TALAPRO-2 study showed a statistically significant improvement in radiographic progression-free survival for TALA + ENZA vs PBO + ENZA (HR=0.45; 95% CI, 0.33–0.61; P <0.0001) in men with HRR-deficient mCRPC. Prior PRO analyses (data cutoff: Oct 3, 2022) reported no clinically meaningful between-arm differences in any functioning scales and a longer time to definitive deterioration (TTDD) in global health status (GHS)/quality of life (QoL) for TALA + ENZA (median 27.1 mo) vs PBO + ENZA (median 19.3 mo; HR=0.69; 95% CI, 0.49–0.97; P =0.032). Here we report updated (data cutoff: Sep 3, 2024) final PROs for the HRR-deficient cohort. Methods: PROs were assessed at day 1 (baseline) and every 4 wks until wk 53, then every 8 wks until radiographic progression using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25, and worst pain by BPI-SF item 3. Prespecified PRO endpoints included overall mean change from baseline (per longitudinal repeated measures mixed-effects model), time to deterioration (TTD), and TTDD. The clinically meaningful threshold was ≥10 points for EORTC scales, ≥2 points for BPI-SF. Between-arm comparisons of TTD/TTDD were made via stratified log-rank test and Cox proportional hazards models. Results: At extended follow-up, 394/399 patients in the HRR-deficient cohort (n=197, both arms) had completed baseline + ≥1 follow-up PRO score. TALA + ENZA resulted in a numerically longer TTDD in GHS/QoL vs PBO + ENZA (HR=0.766; 95% CI, 0.555–1.057; P =0.1063; median, 34.2 vs 22.1 mo, respectively). HR for TTDD in disease-specific urinary symptoms was 0.684; 95% CI, 0.421–1.113; P =0.1247) for TALA + ENZA vs PBO + ENZA. TTD in worst pain by BPI-SF favored TALA + ENZA vs PBO + ENZA (HR=0.552; 95% CI, 0.325–0.937; P =0.0255). Differences in physical, role, emotional, cognitive functioning scores and pain favored TALA + ENZA vs PBO + ENZA, but did not meet the clinically meaningful threshold (Table). Conclusions: With extended follow-up, treatment differences favoring TALA + ENZA vs PBO + ENZA were observed in some functioning and symptoms scales. Consistent with prior analyses, overall QoL was maintained in patients with HRR-deficient mCRPC receiving initial treatment with TALA + ENZA in TALAPRO-2. Clinical trial information: NCT03395197 . QLQ-C30 Scale Estimated Mean Difference, TALA + ENZA – PBO + ENZA (95% CI) P Value Functioning GHS/QoL 2.7 (-0.8, 6.2) 0.1294 Physical 5.3 (1.9, 8.7) 0.0022 Role 4.3 (0.0, 8.6) 0.0524 Emotional 4.9 (1.6, 8.2) 0.0038 Cognitive 5.5 (2.0, 9.1) 0.0024 Social 1.9 (-1.7, 5.4) 0.3005 Symptoms Fatigue -1.5 (-5.2, 2.3) 0.4448 Nausea + Vomiting 0.1 (-1.4, 1.6) 0.8936 Pain -8.5 (-12.3, -4.7) <0.0001 Positive values favor TALA + ENZA for GHS/QoL and functioning scales; negative values favor TALA + ENZA for symptoms scales.