140PD Complex epidermal growth factor receptor (EGFR) mutations and responses to tyrosine kinase inhibitors (TKIs) in 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 mutation were screened. The effectiveness of TKIs in patients with complex mutations was retrospectively analyzed. Results: A total of 16,840 subjects were screened, with 5898 positive patients. 187 patients (3.2% of all EGFR mutant patients) had complex EGFR mutations with 95 of advanced lung adenocarcinoma patients were treated with TKIs. The objective response rate (ORR) for patients who had Del-19 + 21L858R (Group A, n = 27), Del-19/21L858R + atypical mutations (Group B, n = 28), double atypical mutations (Group C, n = 20) and complex mutations with primary drug-resistant pattern (Group D, n = 20) were 72.7%, 54.2%, 66.7% and 15.0%, respectively. Median progression free survival (PFS) in the four groups were 18.2 months (95% CI, 12.0 months to 24.4 months), 10.1 months (95% CI, 6.5 months to 13.7 months), 11.1 months (95% CI, 6.8 months to 15.4 months) and 1.4 months (95% CI, 0.2 months to 2.5 months), respectively. Conclusions: These results suggest on the largest sample size that EGFR–TKI therapy is effective in patients with Del-19 + 21L858R, Del-19/21L858R + atypical mutations and double atypical mutations, but less effective in patients with primary drug–resistant pattern. Patients with the Del-19 + 21L858R mutations may therefore benefit more from treatment with first–generation TKIs. Legal entity responsible for the study: Bo Zhang Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.