Background and purpose: To 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 methods: A 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 progressionfree survival (PFS), respectively. Data were pooled using a random-effects model. Results: Seven 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 cavityoropharyngeal 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. Conclusion: Our 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.
included in the biomarker analysis. Baseline characteristics: Chinese, 100%; female, 70.3%; mean age, 57.4 years; EGFR mutations: L858R, 50%; Del19, 42.2%. All patients experienced 1 drug-related AE, most commonly (grouped terms; any grade/3): diarrhea (n¼63/9, 98.4%/14.1%) and rash or acne (n¼52/5, 81.3%/7.8%). SAEs were reported for 15 patients (23.4%), most commonly cerebral infarction (n¼3, 4.7%), malignant neoplasm progression, CNS metastases (both n¼2, 3.1%). Median TTSP was 13.5 months (95% CI: 10.9, 18.0). At baseline, 19 of 42 patients analyzed (45.2%) had additional non-EGFR mutations; 17 (89.5%) progressed/died. Median PFS was 8.1 months in these patients, versus 12.5 months for patients with EGFR-only mutations (HR, 1.72; 95% CI 0.88, 3.36; p¼0.1054). At Visit 3, mutation status had changed from EGFRm+ to EGFR mutation-negative in 33 of 40 patients analyzed (82.5%). Of these, 29 (87.9%) progressed/died; median PFS was 11.0 months versus 5.5 months for patients who remained EGFRm+ (HR, 1.25; 95% CI: 0.47, 3.30; p¼0.6556).
Conclusion:In this analysis, safety data were consistent with the known safety profile of afatinib. Median PFS was twice as long in patients who became EGFR mutation-negative compared with those who remained EGFRm+; however, the difference was not statistically significant. There was no significant difference in PFS for patients with additional non-EGFR versus those with EGFR-only mutations. This exploratory analysis suggests that afatinib has clinical benefit for patients with EGFRm+ NSCLC across all the subgroups assessed.
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