Abstract
Background: Immune checkpoint inhibitors (ICIs) and therapeutic vaccines have emerged as promising immunotherapeutic strategies for solid tumors. However, their comparative efficacy in improving overall survival (OS) remains unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of ICIs and therapeutic vaccines in improving OS in patients with solid tumors. Methods: A comprehensive search was conducted across PubMed, Cochrane Library, Embase, and Clinical Trials.gov for randomized controlled trials (RCTs) published between 1 January 2010 and 31 December 2024. Studies comparing ICIs or therapeutic vaccines against control treatments (placebo, standard of care, or active comparators) in adults with solid tumors were included. The primary outcome was OS, and data were pooled using RevMan (web). Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Thirteen RCTs involving 10,991 participants were included. A total of 5722 of them were treated with therapeutic vaccines or checkpoint inhibitors. Therapeutic vaccines demonstrated insignificant improvement in OS, with a pooled mean difference of 1.89 months (95% CI: -0.54-4.31; P = 0.13), although with homogeneity (I(2) = 0%). ICIs showed a statistically significant OS benefit, with a pooled mean difference of 1.32 months (95% CI: 0.62-2.02; P = 0.0002) and low heterogeneity (I(2) = 12%). Conclusions: Therapeutic vaccines provide a larger but less consistent benefit, whereas ICIs offer modest but more consistent survival advantage. These findings support the need for personalized immunotherapy approaches as well as further research to identify predictive biomarkers and optimize treatment strategies by acquiring deep insights into the TME dynamic and behaviors.