Cetuximab increases the risk of oral mucositis in radiotherapy-treated head and neck cancer compared to cisplatin: a systematic review of randomized controlled clinical trials.

[OBJECTIVE] To evaluate the risk of oral mucositis in cetuximab-plus-radiotherapy compared to cisplatin-plus-radiotherapy in head and neck cancer patients.

[MATERIALS AND METHODS] This PROSPERO-registered systematic review conducted searches through PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and Grey literature (Google Scholar) until March 2025. Therefore, 10 articles were included for the evaluation in this systematic review and meta-analysis. Risk of bias (RoB) was assessed by Rob-2, and meta-analysis was performed (combined relative risk) in subgroups. The assessment of the certainty of evidence was analyzed by GRADE-pro.

[RESULTS] From 4118 reviewed articles, 10 RCTs were included in the systematic review and meta-analysis, and 4329 patients were evaluated. The Rob was predominantly low. The relative risk of oral mucositis was 1.15 (95% CI = 1.03 to 1.29) higher in cetuximab-plus-radiotherapy compared with cisplatin-plus-radiotherapy in head and neck cancer patients (p = 0.010). There was no heterogeneity (p = 0.890, I = 0%) or Rob's publication (p = 0.404). The GRADE-pro analysis was moderate.

[CONCLUSION] Cetuximab plus radiotherapy in head and neck cancer patients increases by 1.15 times the risk of oral mucositis. Clinical trials with preventing strategies for OM in cetuximab-treated patients were necessary.