Real-World Evidence for First-Line afatinib in Advanced Non-Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations Other than G719X/L861Q/S768I.

IntroductionRare epidermal growth factor receptor (EGFR) mutations other than G719X, S768I, and L861Q are infrequently represented in clinical trials. The efficacy of tyrosine kinase inhibitors (TKIs) against these uncommon variants, either alone or in combination with common mutations, remains limited.MethodsWe retrospectively analyzed patients with advanced-stage non-small cell lung cancer (NSCLC) harboring non-major uncommon EGFR mutations who received first-line afatinib between January 2018 and October 2024. Patients with only TKI-sensitive mutations (Del19, L858 R, G719X, S768I, and L861Q) and without additional rare variants were excluded. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoint was the duration of response (DOR).ResultsAmong the 44 patients, 36.4% had solitary non-major uncommon mutations. The overall ORR and the disease control rates were 65.9% and 86.4%, respectively. The ORR by subgroup was 75.0% for patients with non-major uncommon mutations plus EGFR-TKI-sensitive mutations, and 55.0% for patients with dual or solitary uncommon mutations. At a median follow-up time of 21.9 months, the median PFS was 11.5 months (95% CI: 7.5-22.6). Patients with non-major uncommon mutations co-occurring with TKI-sensitive mutations had a longer median PFS (17.7 months; 95% CI: 13.6-NR) than those harboring non-major mutations alone (either single or dual) (9.1 months; 95% CI: 4.6-NR),