Immune Checkpoint Inhibitor Combinations in Advanced Ovarian Cancer: A Systematic Review and Meta-Analysis of...

Immune checkpoint inhibitors (ICIs) have shown limited efficacy in the treatment of ovarian cancer when used alone. This systematic review and meta-analysis evaluated the impact of different combination partners on ICI efficacy.

PubMed, Embase, CENTRAL, and Web of Science were searched until March 2026 for phase III randomized controlled trials (RCTs) of anti-PD-1/PD-L1 combination regimens. Nine fully published trials (N = 7381) were included in the primary analyses; an ICI monotherapy trial and two conference-abstract-only trials were considered in sensitivity analyses. Hazard ratios (HRs) were pooled using random-effects models with pre-specified subgroup analyses by combination partner. Evidence certainty was assessed using GRADE.

Overall, ICI combination therapy significantly improved progression-free survival (PFS) (HR 0.83, 95% confidence interval (CI) 0.73-0.93; I² = 55.8%; p = 0.007). Bevacizumab plus ICI significantly improved progression-free survival (PFS) (k = 4; HR 0.83, 95% CI 0.74-0.93 [Wald-type]; GRADE: Moderate). PARP inhibitor plus ICI also showed a Wald-type PFS improvement (k = 3; HR 0.78, 95% CI 0.63-0.96 [Wald-type]; GRADE: Low), but this was not robust to Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment or inclusion of abstract-only trials (SA5: k = 5; HR 0.85, 95% CI 0.67-1.09; I² = 90.1%). Chemotherapy plus ICI (two avelumab trials) showed no benefit (k = 2; HR 0.96, 95% CI 0.66-1.38). KEYNOTE-B96 demonstrated the first significant overall survival (OS) benefit with an ICI regimen (HR 0.82, 95% CI 0.69-0.97). Funnel plot assessment showed no asymmetry; Egger's test was not formally applied, as the pre-specified threshold of ten trials was not met (descriptive p = 0.81).

ICI combination therapy improved PFS in advanced ovarian cancer, in contrast to earlier syntheses pooling monotherapy and combination regimens. The benefit was most consistent for bevacizumab-based regimens (GRADE: Moderate); the PARP inhibitor-based benefit was less robust (Low), and chemotherapy combinations offered no advantage (Very low). Subgroup differences were not statistically significant and remain exploratory; a partner-specific, biomarker-guided approach is warranted.