Efficacy of cetuximab-based regimens after immune checkpoint inhibitor failure in recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and meta-analysis

BACKGROUND: Evidence guiding treatment after immune checkpoint inhibitor failure in recurrent or metastatic head and neck squamous cell carcinoma is limited. We performed a systematic review and meta-analysis to estimate the efficacy of cetuximab-based second-line therapy in this setting. METHODS: PubMed, Web of Science, Google Scholar, and the Cochrane Library were searched for studies published from January 2014 to January 2026 reporting outcomes of cetuximab-containing therapy after immune checkpoint inhibitor failure. Random-effects meta-analyses were performed for objective response rate, disease control rate, median progression-free survival, and median overall survival. RESULTS: Fourteen studies including 411 patients were included. Among 404 evaluable patients from 13 studies, the pooled objective response rate was 47% (95% CI, 37%-56%). Among 271 patients from 8 studies, the pooled disease control rate was 70% (95% CI, 58%-80%). Pooled median progression-free survival was 4.69 months (95% CI, 3.30-6.67), and pooled median overall survival was 10.71 months (95% CI, 5.15-22.29). Exploratory subgroup analysis demonstrated a numerically higher objective response rate with cetuximab plus chemotherapy than with cetuximab monotherapy; however, this difference was not statistically significant, and disease control rates were comparable. CONCLUSIONS: Cetuximab-based second-line therapy demonstrates clinically meaningful activity after immune checkpoint inhibitor failure, although prospective studies are needed to define optimal patient and regimen selection.