Response to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma with the Rare Epidermal Growth Factor Receptor Mutation S768I: a Retrospective Analysis and Literature Review

Background The rare epidermal growth factor receptor (EGFR) mutation S768I has only been reported sporadically in patients with lung adenocarcinoma (AC). Objective This study aimed to investigate the prevalence of the S768I mutation in Chinese patients with lung AC and to retrospectively analyze the response of S768I mutants to tyrosine kinase inhibitors (TKIs). Patients and Methods A total of 6698 tissue specimens of lung AC were collected from the Department of Pathology of Shanghai Cancer Center of Fudan University between 2013 and 2015 and screened for EGFR mutations. Previously reported cases were combined with our data to evaluate the response of the S768I mutants to TKIs. Results Thirty-five patients (0.52 %, 35/6698) harbored the S768I mutation, including 8 (22.9 %) with just the S768I mutation and 27 (77.1 %) with compound mutations of S768I and other EGFR mutations (including G719X and L858R). The median progression-free survival (PFS) of the 8 cases with available PFS data was 5.0 months (95 % confidential interval: 0.4–9.6 months). We combined our cases with the sporadic cases from 14 previous reports (total 49 cases) to assess the response to TKIs and found that the objective response rate was 40.0 %, 74.9 %, and 60.0 % for S768I-only mutants, S768I+G719X mutants, and S768I+L858R mutants, respectively. Conclusions S786I mutation is rare in lung AC and is frequently accompanied by G719X, L858R, or other EGFR mutations. Patients harboring only the S768I mutation appear to be more sensitive to TKIs than those with the wild-type EGFR. The S768I mutation may increase the sensitivity of G719X to TKIs but not the sensitivity of L858R to TKIs.