Abstract
Introduction
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.
Methods
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.
Results
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 0.68–0.82, p
Discussion
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.
Systematic review registration
https://www.crd.york.ac.uk/prospero/
, identifier CRD420251249507.