SynthesisInternational journal of surgery (London, England)2026
Exploring the efficacy of PARP inhibitors in metastatic castration-resistant prostate cancer with homologous recombination repair alteration: a meta-analysis based on subgroups and reconstructed individual patient data.
Synthesis in International journal of surgery (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The efficacy of immune checkpoint inhibitors in metastatic castration-resistant prostate cancer: A meta-analysis and reconstructed individual patient data analysis.Human vaccines & immunotherapeutics · 2026Pooled it
- Multi-target modulation of the homologous recombination pathway by resveratrol promotes DNA damage repair in POI: integrated network pharmacology, molecular dynamics simulation, and experimental validation.International journal of surgery (London, England) · 2026Article
- Case Report: Niraparib-abiraterone in HRR-mutated metastatic castration-resistant prostate cancer: clinical insights from five cases.Frontiers in oncology · 2026Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatment for metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) alteration remains a challenge. Recently published trials have evaluated the poly (ADP-ribose) polymerase inhibitors (PARPIs) in mCRPC. However, the efficacy in subgroup with specific HRR gene mutation and treatment protocol requires further elucidation. This meta-analysis aims to explore the efficacy of PARPIs based on subgroups and reconstructed individual patient data (IPD).
methodsLiterature was searched using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to April 2025. The primary outcome was radiographic progression-free survival (rPFS), and the secondary outcomes included overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and adverse events (AEs). Hazard ratios (HRs) and risk ratios (RRs) were pooled as the indicators using inverse-variance and Mantel-Haenszel methods. IPD was reconstructed from Kaplan-Meier curve. Survival analysis was performed using Cox proportional hazards model based on the reconstructed IPD. Heterogeneity was assessed by I 2 and sensitivity analysis. Publication bias was examined via contour‑enhanced funnel plots.
resultsData of 1840 mCRPC patients with HRR alteration from five pivotal phase III clinical trials were analyzed. PARPIs significantly improved overall rPFS (HR: 0.55) and OS (HR: 0.85). PARPIs also prolonged rPFS across the subgroups defined by clinicopathologic features. In BRCA1/2 subgroup, survival benefits were prominent for rPFS (HR 0.32) and OS (HR 0.70). For patients with non- BRCA alterations, no benefits of PARPIs were detected for rPFS and OS in ATM subgroup, and for OS in CDK12 subgroup. Survival analyses indicated that PARPIs treatment was significantly associated with the improved rPFS (HR: 0.73, P < 0.001) and PSA-PFS (HR: 0.80, P = 0.020) in the overall population, and revealed OS benefit in BRCA1/2 subgroup (HR: 0.77, P = 0.030). Comparing with monotherapy, combination regimen of PARPIs provided greater benefits for rPFS (HR: 0.56, P < 0.001)and OS (HR: 0.64., P < 0.001).
conclusionsPARPIsimprove survival in mCRPC patients with BRCA1/2 mutation, but have no effect in those with ATM mutation. Comparing with PARPIs monotherapy, the combination regimen provides greater survival benefit in the overall population. Future investigation should validate these findings in real-world settings.
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