Abstract
BACKGROUND: Despite multiple clinical trials, the benefits and safety of epidermal growth factor (EGF)/EGF receptor (EGFR) vaccines in EGFR-driven solid tumors remain unclear due to small sample sizes and heterogeneous study designs. This systematic review and meta-analysis aimed to evaluate their efficacy and safety. METHODS: We conducted pairwise and single-arm meta-analyses following PRISMA guidelines (PROSPERO: CRD420251026774). Searches in PubMed, Embase, and Cochrane Library identified 26 trials (2701 participants). The primary endpoint was overall survival (OS), with secondary analyses of progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Statistical analyses were performed using R software, with fixed or random-effects models per heterogeneity (I(2)). RESULTS: Compared with best supportive care, vaccine monotherapy significantly improved long-term OS in NSCLC and GBM (3-year OR = 2.16, 5-year OR = 3.20) and prolonged median OS in NSCLC (HR = 0.76). In single-arm studies, NSCLC patients receiving vaccine monotherapy had a 1-year OS of 64% (75% in first-line maintenance), with an ORR of 2% and DCR of 31%. For GBM, vaccine combination therapy improved 3-year OS (OR = 2.42) and 2-year PFS (OR = 1.63) versus standard therapy. Single-arm combination analyses showed an overall 1-year OS of 84%, ORR of 42%, and DCR of 87%, while NSCLC first-line combination achieved a 1-year OS of 85% and DCR of 89%. Notably, EGFR-mutant NSCLC patients had a pooled ORR of 65% and DCR of 98%. Common TRAEs were grade 1-2 (injection site reactions, fever, headache, and vomiting), and combination therapy had no new or severe toxicities. CONCLUSIONS: EGF/EGFR vaccines may improve survival in EGFR-driven solid tumors, particularly NSCLC and GBM. Monotherapy enables long-term disease control, and combination therapy enhances efficacy without added toxicity, supporting further clinical validation. TRIAL REGISTRATION: PROSPERO CRD420251026774.