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  • Title: Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan.
    Author: Hsu PC, Lee SH, Chiu LC, Lee CS, Wu CE, Kuo SC, Ju JS, Huang AC, Li SH, Ko HW, Yang CT, Wang CC.
    Journal: Target Oncol; 2023 Mar; 18(2):195-207. PubMed ID: 36805452.
    Abstract:
    BACKGROUND: Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. OBJECTIVE: We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. PATIENTS AND METHODS: Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. RESULTS: Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI, 20.22-36.77) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355-0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable. CONCLUSIONS: First-line afatinib therapy is effective and safe for advanced lung adenocarcinoma harboring uncommon EGFR mutations. The G719X mutation was an independent factor associated with a favorable outcome. Poor performance (ECOG PS ≥ 2), brain metastasis, and liver metastasis were predictive factors of shorter PFS with first-line afatinib therapy.
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