A meta-analysis published in JAMA Network Open has confirmed that first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy after platinum-based chemotherapy significantly prolongs progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC). However, no overall survival (OS) benefit was observed, and toxicity varied across agents.
The systematic review and meta-analysis, led by Dr Stamatios Petousis and colleagues, included seven randomized clinical trials involving 4013 patients with advanced-stage EOC who had responded to first-line platinum-based chemotherapy.
Progression-Free Survival Benefit Confirmed
PARP inhibitor maintenance therapy was associated with a 43% reduction in the risk of progression or death compared with chemotherapy alone (hazard ratio [HR], 0.57; 95% CI, 0.46–0.70; high certainty).
PFS improvements were seen across most molecular subgroups, including patients with BRCA variants (HR, 0.40; 95% CI, 0.35–0.45), BRCA wild-type disease (HR, 0.62; 95% CI, 0.44–0.86), and homologous recombination–deficient (HRD) tumours (HR, 0.44; 95% CI, 0.39–0.50).
No benefit was seen among those with homologous recombination–proficient (HRP) tumours.
The PFS advantage was consistent regardless of surgical timing, response to chemotherapy, or residual disease.
No Overall Survival Advantage
No molecular subgroup demonstrated a statistically significant OS benefit. The authors noted that although PFS gains were consistent, the lack of OS improvement underscores the importance of assessing long-term clinical value.
Toxicity and Regimen Variability
High-grade adverse events occurred more frequently with PARP inhibitors (HR, 2.40; 95% CI, 1.16–4.93).
Efficacy and toxicity varied across individual agents:
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Senaparib: RR 0.53 (95% CI, 0.40–0.70) for recurrence or death
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Olaparib: RR 0.83 (95% CI, 0.68–1.00)
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Veliparib: RR 1.15 (95% CI, 0.64–2.06) for high-grade adverse events
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Niraparib: RR 4.73 (95% CI, 2.77–8.07) for high-grade adverse events
Clinical Implications
The authors concluded:
“The lack of overall survival benefit, increased toxic effects and variability across subgroups and regimens suggest that treatment should be individualized.”
The findings support continued use of PARP inhibitors in BRCA-mutated and HRD-positive disease but empshasise the need for precision in patient selection and careful management of treatment-related toxicity.
Paper: Petousis S, Kahramanoglu I, Appenzeller-Herzog C, et al. PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2025;8(11):e2541648. doi:10.1001/jamanetworkopen.2025.41648 Access online here.
