Efficacy and safety of cetuximab-based versus platinum-based chemoradiation in HNSCC: evidence from a meta-analysis of 10 randomized controlled trials

Abstract

Background: Platinum-based chemoradiotherapy (CTRT) is the standard treatment for head and neck squamous cell carcinoma (HNSCC). While cetuximab-based radiotherapy (CxRT) has been proposed as an alternative, its efficacy remains controversial. Multiple meta-analyses have compared CxRT with CTRT for HNSCC though they combined randomized controlled trials (RCTs) with lower-evidence studies, compromising result validity. This study presents the first meta-analysis using exclusively RCT data, providing the highest level of evidence for clinical decision-making. Methods: We systematically searched MEDLINE, Embase, Cochrane, and SCOPUS, identifying 10 RCTs (n = 2,557 patients). Primary outcomes included overall survival (OS), disease-free survival (DFS), and all-cause mortality; secondary outcomes were Grade ≥ 3 toxicities. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random effect models. Results: CxRT was associated with a 50% higher recurrence risk (HR 1.50, 95% CI 1.07–2.10) and 27% increased all-cause mortality (OR 1.27, 95% CI 1.05–1.55) compared to CTRT. OS did not differ significantly (HR 1.33, 95% CI 0.79–2.22). Toxicity profiles varied: CxRT had higher mucositis (OR 1.17, 95% CI 1.04–1.32) and skin rash (OR 3.46, 95% CI 1.28–9.36), while CTRT showed more anemia (OR 0.15, 95% CI 0.05–0.52) and nausea/vomiting (OR 0.31, 95% CI 0.19–0.53). Conclusion: CxRT is inferior to CTRT in HNSCC, with poorer disease control and survival outcomes. The lack of biomarker (EGFR/RAS) stratification in trials may have contributed to suboptimal patient selection. While CxRT may be an option for cisplatin-ineligible patients, platinum-based therapy appears to be the standard. Future research should optimize cetuximab’s role through biomarker-driven selection. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2025.