PARP inhibitor-based combinations in first-line metastatic castration-resistant prostate cancer: A meta-analysis.

Authors

Wala Ben Kridis, Afef Khanfir

Published in

Urologic oncology. Nov 10, 2026. Epub Nov 10, 2026.

Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors combined with androgen receptor pathway inhibitors (ARPIs) have emerged as a promising therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC). We performed a systematic review and meta-analysis of phase III studies evaluating PARP inhibitor-ARPI combinations in the first-line mCRPC setting. PubMed/MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were systematically searched. Eligible studies were randomized phase III trials comparing a PARP inhibitor plus an ARPI with the corresponding ARPI-based control regimen in first-line mCRPC. The primary endpoint was progression-free survival (PFS), while overall survival (OS) was a key secondary endpoint. Three phase III trials (PROpel, MAGNITUDE, and TALAPRO-2) comprising 2,024 patients were included. PARP inhibitor-ARPI combinations significantly improved PFS compared with ARPI-based therapy alone (HR 0.66, 95% confidence interval [CI] 0.58-0.76; P < 0.001), corresponding to a 34% reduction in the risk of progression or death. A significant OS benefit was also observed (HR 0.79, 95% CI 0.70-0.89; P < 0.001), representing a 21% reduction in mortality risk. Heterogeneity was absent for both endpoints (I² = 0%). In patients with BRCA1/2 alterations, treatment effects were more pronounced, with pooled HRs of 0.40 (95% CI 0.31-0.53) for PFS and 0.55 (95% CI 0.42-0.71) for OS. Combination therapy was associated with increased hematologic toxicity, particularly anemia, but adverse events were generally manageable. PARP inhibitor-ARPI combinations significantly improve progression-free and OS in first-line mCRPC, with the greatest benefit observed in BRCA1/2-altered tumors.

PMID:
43009426
Bibliographic data and abstract were imported from PubMed on 11 Nov 2026.

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