Complex epidermal growth factor receptor mutations and their responses to tyrosine kinase inhibitors in previously untreated advanced lung adenocarcinomas

Abstract

BACKGROUND: Two or more different epidermal growth factor receptor (EGFR) mutations can be detected within a single tumor sample, which represents complex mutations. However, the frequency and efficacy of tyrosine kinase inhibitor (TKI) treatments for patients harboring these mutations are unknown. METHODS: From January 2011 to January 2017, patients diagnosed with EGFR mutations were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed. RESULTS: A total of 16,840 subjects were screened, and there were 5898 positive patients. One hundred eighty-seven patients (3.2% of all patients with EGFR mutations) had complex EGFR mutations, and 51 of the patients with advanced adenocarcinoma were treated with TKIs as a first-line treatment. The objective response rates for patients who had Del-19+21L858R mutations (n = 15), Del-19/21L858R+atypical mutations (n = 16), double atypical mutations (n = 8), and complex mutations with a primary drug-resistant pattern (n = 12) were 75.0%, 60.0%, 71.0%, and 8.3%, respectively. The median progression-free survival times for the 4 groups were 18.2 months (95% confidence interval [CI], 10.6-25.9 months), 9.7 months (95% CI, 3.3-15.8 months), 9.6 months (95% CI, 3.3-19.0 months), and 1.4 months (95% CI, 0.4-2.3 months), respectively. CONCLUSIONS: These results from the largest sample size suggest that EGFR-TKI therapy is effective in patients with Del-19+21L858R mutations, Del-19/21L858R+atypical mutations, and double atypical mutations but is less effective in patients with a primary drug-resistant pattern. Patients with the Del-19+21L858R mutations may, therefore, benefit more from treatment with first-generation TKIs. Cancer 2018;124:2399-406. © 2018 American Cancer Society.