Concurrent gene alterations with EGFR mutation and treatment efficacy of EGFR-TKIs in Chinese patients with non-small cell lung cancer

PURPOSE We investigated the frequency of concurrent genes in EGFR-mutant non-small cell lung cancer patients and determined its value in predicting the efficacy of EGFR-TKIs treatment. METHODS Three hundred and twenty patients, who harbored EGFR activating mutations and received EGFR-TKIs treatment, were examined for another eight genes including KRAS, NRAS, PIK3CA, BRAF, and HER2 mutations and ALK, ROS1, and RET fusion genes based on reverse transcription PCR. Progression-free survival and overall survival with EGFR-TKIs treatment were evaluated using Kaplan-Meier methods and compared between different patients using log-rank tests. RESULTS Twenty-one (6.6%) of 320 EGFR mutant samples with additional gene alterations were identified. The most common concurrent gene was PIK3CA mutation (n = 9), followed by EML4-ALK rearrangement (n = 6), HER2 mutation (n = 3), RET rearrangement (n = 1), ROS1 rearrangement (n = 1) and KRAS mutation (n = 1). Patients with single EGFR mutation had a significantly longer progression-free survival than those with concurrent genes (10.9 vs. 6.0 months, P = 0.002). Among the 21 cases, patients with PIK3CA mutation had the longest median progression-free survival (7.6 months), followed by ALK rearrangement (5.0 months) and other gene types (1.2 months). No overall survival difference was found between patients with single EGFR mutation and concurrent gene alterations (21.0 vs.17.6 months, P = 0.17). CONCLUSION We demonstrated that concurrent gene alterations occurred in some patients with EGFR mutations. Concurrent gene alterations decreased the efficacy of EGFR-TKIs.