To analyze the clinicopathological features of uncommon epidermal growth factor receptor (EGFR)mutations in non-small cell lung cancer(NSCLC) and the therapeutic efficacy of first-line tyrosine kinase inhibitors(TKI).

All of 51 patients with uncommon EGFR mutation in stage Ⅲb-Ⅳ NSCLC treated in our hospital from August 2017 to July 2023 were selected. The clinicopathological characteristics were analyzed. According to treatment methods, it was divided into TKI treatment group (42 cases), chemotherapy group (5 cases) and palliative treatment group (4 cases). Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were analyzed.

Among the 51 patients with uncommon mutations, 12 had 20 exon insertions (20 ins), 21 had major uncommon mutations, and 18 had complex mutations. There were 11 cases (22%) of uncommon mutation L861Q and 8 cases (16%) of uncommon complex mutation G719X+ S768I. The ORR of the chemotherapy group was 20%, lower than that of the targeted therapy group, which was 38.1%. TKI treatment for major uncommon mutations (mPFS=16 months, IQR 9-21; mOS=19 months, IQR 14-28) and complex mutations (mPFS=15 months, IQR 8-20; mOS=20 months, IQR 15~25) showed better efficacy. TKI treatment was less effective for 20 ins (mPFS=4 months, IQR 2-7; mOS=6 months, IQR 3~7). Chemotherapy for major uncommon mutations and complex mutations (mPFS=6 months, IQR 1-12; mOS=16 months, IQR 15-19) was better than TKI treatment(P<0.001).

Specific types of uncommon mutations in NSCLC patients with uncommon EGFR mutations have significant implications for treatment response and survival. Patients with major uncommon mutations and uncommon compound mutations demonstrated prolonged progression-free survival and overall survival when treated with TKIs, whereas patients with 20 exon insertions showed a suboptimal response to TKI treatment.