PARP Inhibitor Plus Androgen-receptor Signaling Inhibitor Versus the Same Inhibitor Alone in Homologous-Recombination-Repair-Altered Metastatic Prostate Cancer Across the Hormone-Sensitive and Castration-Resistant Continuum: A Systematic Review and Meta-Analysis
In brief
PARP inhibitor plus AR blocker halves radiographic progression risk in HRR-altered prostate cancer
A meta-analysis of five phase III trials (2,343 men) found that adding a PARP inhibitor to standard androgen-receptor signaling therapy reduced radiographic progression-free survival events by roughly 44% overall, with an even larger 64% reduction in BRCA-altered tumors. Overall survival showed a modest signal but remains immature, and severe side-effects were more common, so benefits must be weighed against toxicity.
- Journal
- Clinical genitourinary cancer (Q1)
- Published
- 23 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Yanfeng Su, Ruji Wu, Huien Pan, Haofeng Yuan
- PMID
- 42586923
- DOI
- 10.1016/j.clgc.2026.102629
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 16 August 2026): PARP+ARSI improves rPFS in HRR‑altered mPC
- Picked for Urology (top studies of the week, 16 August 2026): PARPi+ARSI improves rPFS in HRR-altered metastatic prostate cancer
Abstract
PARP inhibitors (PARPi) combined with androgen-receptor signaling inhibitors (ARSI) improve radiographic progression-free survival (rPFS) in homologous-recombination-repair (HRR)-altered metastatic prostate cancer, but effects across disease states and genomic subgroups remain uncertain. We searched MEDLINE, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov through June 2026 for randomized trials of PARPi plus ARSI versus the same ARSI alone in HRR-altered metastatic prostate cancer. Trial-level log hazard ratios were pooled using REML random-effects models with Hartung-Knapp confidence intervals. Disease-state and BRCA/non-BRCA comparisons, including a paired ratio-of-hazard ratios [HRs] analysis, were exploratory. Five phase III trials included 2343 men. PARPi plus ARSI improved rPFS overall (HR 0.56, 95% confidence intervals 0.43-0.72). Pooled HRs were 0.36 (0.21-0.63) for BRCA-altered disease and 0.75 (0.51-1.09) for the heterogeneous non-BRCA group. The exploratory paired BRCA/non-BRCA ratio of HRs was 0.54 (0.32-0.90; P = .031), assuming zero covariance. Disease-state estimates were imprecise (mHSPC 0.56, 0.10-3.11; mCRPC 0.55, 0.29-1.07). The latest pooled overall-survival estimate was 0.75 (0.61-0.93; I² = 25%), but 2 trials remained interim. Grade ≥ 3 adverse events were consistently increased. PARPi plus ARSI improves rPFS in HRR-altered metastatic prostate cancer. The relative effect appears larger in BRCA-altered disease, but the interaction remains exploratory and non-BRCA alterations are biologically heterogeneous. Disease-state estimates do not support comparative inference. Overall-survival evidence suggests a signal, not definitive benefit, and must be balanced against increased toxicity.
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.