Objective: To-evaluate the role and clinical value of cetuximab in the treatment of head and neck squamous cell carcinoma (HNSCC), and figure out its effectiveness and application, so as to develop evidence-based recommendations for treatment.

Method: We comprehensively searched the CBM, Pubmed, EMBASE, and the Cochrane databases to identify published studies on the effect of cetuximab in HNSCC patients. Primary outcomes included overall survival (OS), progression-free survival(PFS) and overall response rate(ORR). Secondary outcomes included serious adverse events, such as neutropenia, anemia, thrombocytopenia, skin reactions, hypokalemia, vomiting, asthenia, hypomagnesemia, dyspnea and sepsis. Results were dispalyed as risk ratio (RR), odds ratio (OR), mean difference (MD) and 95% CI.

Result: A Meta-analysis was conducted on 4 randomized controlled trials, including 2 trials comprising 1,319 patients with locally advanced HNSCC and 2 trails comprising 559 patients with recurrent or metastatic HNSCC. For locally advanced HNSCC, the 2 year PFS and OS showed no significant differences in patients received cetuximab or not (PFS fixed effect: RR=1.02, 95%CI 0.92-1.12, P>0.05; OS fixed effect: RR=1.06, 95%CI 1.00-1.13, P>0.05, respectively). Grade 3-4 dysphagia was also similar in patients treated with cetuximab or no cetuximab (dysphagia: fixed effect: RR = 0.92; 95% CI 0.84-1.02, P>0. 05). Only grade 3-4 mucositis and skin reaction showed statistical significance between patients treated with cetuximab and patients with no cetuximab (mucositis: fixed effect: RR=1.21; 95%CI 1.07-1. 36, P<0. 05; skin reaction: fixed effect: RR=1.99; 95%CI 1.39-2.85, P<0.05, respectively). For recurrent or metastatic HNSCC, the OS overall mean difference was 2.41 (95% CI 0.96-3.86, P<0.05), the PFS overall mean difference was 2. 06 (95% CI 1.34 - 2.77, P<0.05), and the ORR overall Odds ratio was 2.38 (95% CI 1.60-3.54,P<0.05), suggesting significant effect of cetuximab in improving the prognosis of R/M HNSCC. Owing to small number of trials it was not possible to assess the presence of publication bias. Of note, the 1 year survival overall Odds ratio was 1.39 (95% CI 0.98-1.97, P>0.05). The grade 3 or 4 adverse effects were described in 83. 4% of patients in cetuximab group and 75. 5% of patients in no cetuximab group. The overall side effects risk ratio suggested statistically significant difference between patients treated with cetuximab and pa- tients with no cetuximab (RR=1.11, 95% CI 1.01-1.20, P<0.05, P =47%).

Conclusion: The 2 year progression-free survival and overall survival were similar between cetuximab group and no cetuximab group in patients with locally advanced head and neck squamous cell cancer. Data are limited and the benefits of cetuximab on this outcome remain uncertain. Impact of grade 3-4 dysphagia was similar in both groups, however, the incidence of grade 3-4 mucositis and skin reaction were lower in patients treated with cetuximab. Existing randomized controlled trials provided a scientific evidence for the use of cetuximab in R/M HNSCC. The conclusion of the study is based on limited number of RCT, so further investigation is still needed before firm recommendations of cetuximab can be made in the treatment of HNSCC.