Final patient-reported outcomes (PROs) in unselected men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as initial treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from the phase 3 TALAPRO-2 study.

Abstract

11120 Background: TALAPRO-2 demonstrated statistically significant improvement with TALA + ENZA vs PBO + ENZA in radiographic progression-free survival (primary endpoint; HR=0.63; 95% CI, 0.51–0.78; P <0.0001) in unselected men with mCRPC. Prior PRO analyses (data cutoff: Aug 16, 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 30.8 mo) vs PBO + ENZA (25.0 mo; HR=0.780; 95% CI, 0.62–0.99; P =0.038). Here we report updated (data cutoff: Sep 3, 2024) final PROs for the unselected cohort. Methods: PROs were assessed at day 1 (baseline) and scheduled visits (every 4 weeks until week 53, and then every 8 weeks) 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 analyses 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 and ≥2 points for BPI-SF. Between-arm comparisons of TTD/TTDD were made using a stratified log-rank test and a Cox proportional hazards model. Results: Of the 805 men randomized to treatment, 793 (TALA + ENZA, n=395; PBO + ENZA, n=398) had 1 baseline + ≥1 follow-up PRO score. With extended follow-up, median TTDD for GHS/QoL in the TALA + ENZA arm was 41.5 mo vs 34.1 mo in the PBO + ENZA arm (HR=0.878; 95% CI, 0.704–1.096; P =0.2487). Median TTDD for urinary symptoms in the TALA + ENZA arm was 59.8 mo vs 58.0 mo in the PBO + ENZA arm (HR=0.861; 95% CI, 0.622–1.191; P =0.3655). No clinically meaningful between-arm differences in QLQ-C30 functioning and symptoms scales were observed (Table). No between-arm difference in TTD for worst pain by BPI-SF was observed. Conclusions: With extended follow-up, QoL was maintained with TALA + ENZA. These data confirm that QoL is not compromised when TALA is added to ENZA, for initial treatment of unselected men with mCRPC. Clinical trial information: NCT03395197 . QLQ-C30 Scale Estimated Mean Difference, TALA + ENZA – PBO + ENZA (95% CI) P Value Functioning GHS/QoL -2.2 (-4.3, -0.1) 0.0382 Physical -1.6 (-3.9, 0.7) 0.1663 Role -1.7 (-4.2, 0.9) 0.2009 Emotional -0.9 (-2.7, 1.0) 0.3620 Cognitive -0.9 (-3.0, 1.1) 0.3791 Social -0.9 (-2.9, 1.2) 0.4088 Symptoms Fatigue 2.4 (0.1, 4.7) 0.0437 Nausea + Vomiting 0.8 (-0.1, 1.6) 0.0723 Pain -0.8 (-3.3, 1.7) 0.5270 Positive values favor TALA + ENZA for GHS/QoL and functioning scales; negative values favor TALA + ENZA for symptoms scales.