Clinical outcomes of lung adenocarcinoma patients harboring uncommon epidermal growth factor receptor (EGFR) mutations treated with EGFR-tyrosine kinase inhibitors (TKIs)

Background: This study aimed to explore the efficacy of different epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (AC) patients harboring uncommon EGFR mutations. Methods: Between January 1st, 2013 and October 1st, 2019, 2,680 EGFR mutation-positive patients with confirmed stage IIIB/IV lung AC were enrolled from Zhejiang Cancer Hospital. Uncommon EGFR mutations were detected in 132 patients using next-generation-sequencing. Clinicopathological features between patients with uncommon EGFR mutations and common EGFR mutations were evaluated by the chi-square test. The clinical outcomes of patients with uncommon EGFR mutations were analyzed by the Kaplan-Meier method. Results: Of 132 AC patients with uncommon EGFR mutations, 115 received EGFR-TKIs. Second-generation EGFR-TKIs were associated with longer progression-free survival (PFS) (P=0.116) and overall survival (OS) (P=0.005) than first or third-generation EGFR-TKIs. We also found that patients with compound mutations and double uncommon EGFR mutations had longer PFS (P=0.725) and OS (P=0.741) than those with single uncommon EGFR mutation, although the difference was not significant. In addition, third-generation EGFR-TKIs were more effective than the other two agents in patients with primary T790M, mutation regarding PFS (P=0.150) and OS (P=0.033), although the difference in PFS was not significant. Conclusions: Patients with uncommon EGFR mutations treated with second-generation EGFR-TKIs showed better PFS and OS. EGFR-TKIs were more effective in patients with compound mutations or double uncommon mutations.