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.
Yanfeng Su, Ruji Wu, Huien Pan et al.
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In 30 seconds
This systematic review and meta-analysis evaluated the efficacy of PARP inhibitors combined with androgen-receptor signaling inhibitors (ARSI) in 2343 men with homologous-recombination-repair-altered metastatic prostate cancer. The combination therapy significantly improved radiographic progression-free survival (rPFS) with a hazard ratio of 0.56 (95% CI 0.43-0.72).
Key findings
- PARP inhibitor plus ARSI improved rPFS overall with a hazard ratio of 0.56.
- For BRCA-altered disease, the pooled hazard ratio was 0.36.
- The exploratory paired BRCA/non-BRCA ratio of HRs was 0.54.
- Grade ≥ 3 adverse events were consistently increased with combination therapy.
Why it matters
The findings suggest that combining PARP inhibitors with ARSI may enhance treatment outcomes in specific genomic subgroups of metastatic prostate cancer, particularly in BRCA-altered cases. However, clinicians must weigh the potential benefits against the increased risk of adverse events.