The primary site of head and neck squamous cell carcinoma predicts survival benefits of EGFR inhibitors: A systematic review and meta-analysis

Background and purposeTo assess the survival benefits associated with epidermal growth factor receptor (EGFR) inhibitors in head and neck squamous cell carcinoma (HNSCC) according to the primary site.Materials and methodsA systematic review and meta-analysis were conducted for randomized phase III trials comparing treatment with or without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCC. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Data were pooled using a random-effects model.ResultsSeven trials with a total of 3391 patients were included. The addition of EGFR inhibitors improved OS in patients with oral cavity-oropharyngeal carcinoma (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.67–0.87, P < 0.001) but not in patients with hypopharyngeal-laryngeal carcinoma (HR 0.94, 95% CI 0.82–1.08, P = 0.398). A significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.029). The addition of EGFR inhibitors increased PFS in both patients with oral cavity-oropharyngeal carcinoma (HR 0.67, 95% CI 0.52–0.85, P = 0.001) and patients with hypopharyngeal-laryngeal carcinoma (HR 0.81, 95% CI 0.69–0.94, P = 0.005). A trend towards significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.161). Comparable results were observed in the pre-specified subgroup analyses. Meta-regression analyses suggested that the primary site appeared to be a predictor of survival benefits in HNSCC patients who received treatment with EGFR inhibitors over those who did not.ConclusionOur meta-analysis suggests that the survival benefits of EGFR inhibitors might depend on primary sites in HNSCC. Further studies are needed to confirm this finding.