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.
Boldes et al. (Sat,) studied this question.
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