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Life sciences · Review
Cancers · September 14, 2026
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Background/Objectives: 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. Methods: 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. Results: 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). Conclusions: 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.