{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:07:10Z","timestamp":1789391230872,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u20130.93; I2 = 55.8%; p = 0.007). Bevacizumab plus ICI significantly improved progression-free survival (PFS) (k = 4; HR 0.83, 95% CI 0.74\u20130.93 [Wald-type]; GRADE: Moderate). PARP inhibitor plus ICI also showed a Wald-type PFS improvement (k = 3; HR 0.78, 95% CI 0.63\u20130.96 [Wald-type]; GRADE: Low), but this was not robust to Hartung\u2013Knapp\u2013Sidik\u2013Jonkman (HKSJ) adjustment or inclusion of abstract-only trials (SA5: k = 5; HR 0.85, 95% CI 0.67\u20131.09; I2 = 90.1%). Chemotherapy plus ICI (two avelumab trials) showed no benefit (k = 2; HR 0.96, 95% CI 0.66\u20131.38). KEYNOTE-B96 demonstrated the first significant overall survival (OS) benefit with an ICI regimen (HR 0.82, 95% CI 0.69\u20130.97). Funnel plot assessment showed no asymmetry; Egger\u2019s 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\u2013based 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.<\/jats:p>","DOI":"10.3390\/cancers18182971","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"2971","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune Checkpoint Inhibitor Combinations in Advanced Ovarian Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"18","author":[{"given":"Boram","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-2116","authenticated-orcid":false,"given":"Youn Jin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9005-7796","authenticated-orcid":false,"given":"Keun Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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