Survival benchmarking of talazoparib plus enzalutamide in homologous recombination repair-deficient metastatic castration-resistant prostate cancer: a reconstructed individual patient data analysis.

Homologous recombination repair (HRR) alterations define a heterogeneous subgroup of metastatic castration-resistant prostate cancer. TALAPRO-2 established randomized benefit of talazoparib plus enzalutamide within HRR-deficient disease, but it did not determine whether treated HRR-deficient patients remain prognostically disadvantaged relative to biomarker-defined enzalutamide-alone reference groups. We performed exploratory trial-internal benchmarking using reconstructed individual patient data from published TALAPRO-2 Kaplan-Meier curves, with different endpoint-specific reference groups for radiographic progression-free survival (rPFS) and overall survival (OS). With enzalutamide alone, HRR-deficient disease had shorter rPFS than HRR-non-deficient disease (16.4 vs 22.3 months; HR 1.42, 95% CI 1.00-2.00) and shorter OS than disease with no HRR alteration detected (30.9 vs 37.7 months; HR 1.23, 95% CI 0.89-1.71). With talazoparib plus enzalutamide, corresponding medians were 27.9 and 45.8 months; cross-benchmark HRs were 0.73 (95% CI 0.50-1.07) and 0.66 (95% CI 0.46-0.96). These non-randomized comparisons are descriptive and do not establish equivalence, superiority, or prognostic normalization.