Phase II study of afatinib for advanced non-small cell lung cancer with uncommon epidermal growth factor receptor mutations, including compound mutations detected by next-generation sequencing.

Background: There are no prospective clinical data on the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring various uncommon epidermal growth factor receptor (EGFR) mutations detected using next-generation sequencing. We aimed to report the efficacy and safety of afatinib in patients with NSCLC harboring uncommon EGFR mutations detected using next-generation sequencing.

Methods: This was a prospective single-center single-arm phase II study. Patients with histologically confirmed metastatic or recurrent NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion and T790M mutations detected using next-generation sequencing, were eligible. Patients received oral afatinib (40 mg once daily). The primary endpoint was the objective response rate. The secondary endpoints were progression-free survival, overall survival, and safety.

Results: Between August 2019 and September 2022, 17 patients were enrolled. The median age was 71 years (range, 59-80 years; 9 males). The uncommon mutations identified were G719X (n = 4; 24%), S768I (n = 3; 17.6%), and L861Q (n = 6; 35%), and 13 other rare EGFR mutations were detected in 10 patients. These mutations were identified as single or compound mutations. The objective response rate for all patients was 82.4%, median progression-free survival was 11.3 months, and median overall survival was 27.8 months. Grade 3 or higher adverse events were diarrhea (n = 5; 29%), paronychia (n = 2; 12%), and decreased appetite (n = 2; 12%). All adverse events were manageable, and there were no treatment-related deaths.

Conclusions: Afatinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.