Clinical efficacy and challenges of cancer-testis antigen vaccines in advanced solid tumors: A systematic review and meta-analysis.

Cancer-testis antigens (CTA) vaccines are being actively explored for advanced solid tumors, yet their clinical value remains uncertain. We conducted a systematic review and meta-analysis to December 21, 2024, synthesizing single-arm outcomes (objective response rate [ORR], disease control rate [DCR]) and randomized evidence for overall survival (OS) and disease-free survival (DFS) using random-effects models. Across 73 single-arm trials (n = 1435), the pooled ORR was 13.0 % (95 % CI 11.0-16.0; I²=32.7 %) and the DCR was 39.0 % (95 % CI 34.0-44.0; I²=6.5 %); higher ORRs were seen in melanoma (16.2 %), with intravenous administration (22.4 %), and with dendritic-cell platforms (19.3 %). In 12 randomized trials, vaccination was associated with a modest improvement in OS (HR 0.80, 95 % CI 0.66-0.97; I²=39.3 %) but showed no significant difference in DFS (HR 0.98, 95 % CI 0.89-1.08; I²=0 %). Leave-one-out analyses were stable and Egger's test did not suggest small-study effects (OS p = 0.315). Grade ≥ 3 adverse events occurred in 29.2 % of patients, more often with combination therapy (35.4 %) than monotherapy (22.7 %); fatigue, rash, and fever were most common. Overall, CTA vaccination demonstrates modest antitumor activity with manageable toxicity, while heterogeneity by platform and route underscores the need for larger, contemporary randomized trials to refine indications.