{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:27Z","timestamp":1788761307945,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Introduction<\/jats:title>\n Immunotherapy has reshaped the adjuvant landscape, with several immune checkpoint inhibitors (ICIs) approved in different tumor types. This meta-analysis evaluates the benefit of adjuvant ICIs across solid tumors.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A systematic literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the proceedings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) was performed from January 2015 to June 2026 in accordance with PRISMA to identify phase II and III randomized controlled trials (RCTs) testing ICIs versus non-ICI controls in the adjuvant setting. Trials with a single arm, local treatments, or combinations of ICIs with non-ICI systemic treatments (including chemotherapy, radiotherapy, targeted therapies, or vaccines) were excluded. Eligible comparisons included ICI-based adjuvant strategies versus randomized comparator arms defined by the original trial design. Trials comparing an ICI strategy with an alternative active immunotherapy regimen were considered eligible when the experimental intervention represented the ICI strategy under evaluation and the comparator reflected the established standard of care. Dual-checkpoint blockade regimens consisting exclusively of immune checkpoint inhibitors were considered eligible and analyzed separately. Hazard ratios (HRs) for recurrence-related outcomes (DFS\/RFS\/PFS) and overall survival (OS) were pooled using random-effects models. A sensitivity analysis restricted to phase III trials was performed to evaluate the robustness of the primary findings. Subgroup analyses were conducted by tumor type and ICI mechanism of action.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Twenty-one randomized controlled trials (RCTs), including 17,446 randomized patients across eight different solid tumors, were analyzed. These trials contributed 23 treatment comparisons due to multiple experimental comparisons from IMMUNED and CheckMate 914. Adjuvant ICIs significantly improved DFS\/RFS\/PFS (HR 0.74, 95% CI 0.68\u20130.82, p&lt;0.0001) and OS (HR 0.84, 95% CI 0.78\u20130.90, p&lt;0.0001) compared with non-ICI controls. The DFS\/RFS benefit was observed across several tumor types, including melanoma, urothelial carcinoma, renal cell carcinoma, and NSCLC (HRs 0.65, 0.78, 0.84, and 0.87, respectively). Regarding ICI class, significant DFS\/RFS improvements were observed with CTLA-4, anti\u2013PD-1, and anti\u2013PD-L1 inhibitors (HRs 0.77, 0.69, and 0.89, respectively). Exploratory meta-regression identified a significant overall association between ICI class and treatment effect (QM p = 0.0183; R\u00b2 = 45.2%); however, no individual checkpoint class showed a statistically significant difference compared with the reference category. These findings should therefore be interpreted cautiously and considered hypothesis-generating. Tumor-specific OS benefits were statistically significant in melanoma and urothelial carcinoma (HRs 0.76 and 0.85, respectively), whereas OS effects in other tumor types remain uncertain due to limited data availability and variable follow-up maturity.<\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n Overall, these findings support the efficacy of adjuvant ICIs across multiple solid tumors, with consistent improvements in DFS\/RFS and a significant pooled OS benefit. Exploratory meta-regression suggested that tumor type may contribute to between-study heterogeneity; however, results should be interpreted cautiously given the limited number of studies, trial-level differences, and potential ecological bias.<\/jats:p>\n <\/jats:sec>\n \n Systematic review registration<\/jats:title>\n \n https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n , identifier CRD420251249507.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1903546","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:35:43Z","timestamp":1788759343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant immune checkpoint inhibitors across solid tumors: a meta-analysis of phase II-III randomized trials"],"prefix":"10.3389","volume":"16","author":[{"given":"Mariam Grazia","family":"Polito","sequence":"first","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]},{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisana","family":"Sisca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Caruso","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cosimati","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Adriana","family":"Ramirez Reinaga","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etien","family":"Leka","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science and Biotechnology, Universit\u00e0 \u201cLa Sapienza\u201d","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Paolo","family":"Spinelli","sequence":"additional","affiliation":[{"name":"UOC Oncologia Territoriale \u2013 ASL Latina \u2013 CDS Aprilia, La Sapienza Universit\u00e0 Di Roma Polo Pontino","place":["Latina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","unstructured":"Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial\n \n \n \n Eggermont\n AMM\n \n \n Chiarion-Sileni\n V\n \n \n Grob\n J-J\n \n \n Dummer\n R\n \n \n Wolchok\n JD\n \n \n Schmidt\n H\n \n \n 10.1016\/j.ejca.2019.07.001\n Eur J Cancer\n 119\n 2019","DOI":"10.1016\/j.ejca.2019.07.001"},{"key":"B2","doi-asserted-by":"crossref","unstructured":"Phase III study of adjuvant ipilimumab (3 or 10 mg\/kg) versus high-dose 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