Exploratory Time-Dependent Patterns in Estimated Treatment Effect of Talazoparib Plus Enzalutamide in HRR Non-Deficient or Unknown Metastatic Castration-Resistant Prostate Cancer: A Post Hoc Analysis of the TALAPRO-2 Trial
In brief
Talazoparib-enzalutamide lowers three-year death risk by ~40% in HRR-proficient prostate cancer
In a post-hoc reconstruction of the TALAPRO-2 trial, patients without confirmed HRR deficiency who received talazoparib plus enzalutamide showed a 41% lower hazard of death during the 36-48 month interval, while radiographic progression was delayed early (hazard about 44% lower in the first six months). The analysis is exploratory, without formal proof of a time-varying effect, and should not change practice until confirmed in biomarker-selected studies.
- Journal
- International journal of urology : official journal of the Japanese Urological Association (Q2)
- Published
- 1 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Shugo Yajima, Soichiro Yoshida, Wei Chen, Hiroshi Fukushima, Hajime Tanaka, Hiroyuki Sato, et al.
- PMID
- 42502892
- DOI
- 10.1111/iju.70582
Why clinicians should know about it
- Picked for Geriatrics and Gerontology (paper of the day, 27 July 2026).
- Picked for Urology (paper of the day, 27 July 2026): Exploratory time‑dependent effects of talazoparib plus enzalutamide in prostate cancer
Abstract
OBJECTIVES: Talazoparib plus enzalutamide improved overall survival (OS) in the biomarker-unselected TALAPRO-2 population, but OS benefit was not statistically significant in the homologous recombination repair (HRR) non-deficient or unknown subgroup, whereas radiographic progression-free survival (rPFS) was prolonged. We explored time-dependent patterns in estimated treatment effects in this subgroup. METHODS: Approximate individual-level data for 636 patients were reconstructed from published Kaplan-Meier curves; original trial-level patient data were unavailable. The proportional hazards assumption was assessed using Schoenfeld residuals and log-log plots. Interval-specific hazard ratios (HRs) were estimated using piecewise Cox models. A treatment-by-log(time + 1) interaction was evaluated formally. Sensitivity analyses included alternative interval schemes, landmark analyses, restricted mean survival time (RMST), and descriptive application of the same piecewise framework to the HRR-deficient subgroup. RESULTS: The proportional hazards assumption was not rejected for OS (p = 0.63) or rPFS (p = 0.37). For OS, the 36-48-month interval showed a nominally lower hazard with talazoparib (HR 0.59; 95% confidence interval [CI] 0.36-0.97; nominal p = 0.039). For rPFS, the lowest HR occurred at 0-6 months (HR 0.56; 95% CI 0.37-0.86; p = 0.008). Treatment-by-log(time + 1) interactions were not statistically significant for OS (p = 0.44) or rPFS (p = 0.12). CONCLUSIONS: This reconstructed-data post hoc analysis suggested exploratory time-dependent patterns in effect estimates without formal evidence of a time-varying treatment effect. Findings are descriptive, hypothesis-generating, and should not be extrapolated to molecularly confirmed HRR-proficient disease. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03395197.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.