Optimizing afatinib dosage: enhancing treatment outcomes and minimizing toxicities in advanced EGFR-mutated non-small cell lung cancer patients in Vietnam

Background: Afatinib’s efficacy and dose-adjustment strategies have been validated in clinical trials and increasingly supported by real-world evidence. Objectives: This study aimed to provide additional real-world insights into afatinib use and to assess the impact of initial dosing and subsequent dose modifications on treatment outcomes and tolerability in patients with advanced epidermal-growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Design: We conducted a multicenter retrospective analysis of patients with advanced EGFR-mutated NSCLC who received first-line afatinib between April 2018 and June 2022. Methods: Patients were categorized into four subgroups based on their starting and optimal afatinib doses. The primary endpoints were to analyze the association between afatinib dosing and time-to-treatment failure (TTF), overall survival (OS), and toxicity. Results: A total of 343 patients were included. The most common starting afatinib dose was 30 mg (58.6%), followed by 40 mg (39.9%). The optimal dose maintained during treatment was 30 mg in 62.1% of patients, 40 mg in 33.2%, and 20 mg in 4.7%. Dose reductions due to toxicity occurred in 23.6% of cases. Regarding four subgroups: 53.1% of patients started and remained on <40 mg, 25.4% started and maintained 40 mg, 14.6% started at 40 mg but de-escalated to <40 mg, and 7.0% started <40 mg and escalated to 40 mg. After a median follow-up of 36.8 months, the median OS for all patients was 31.3 months (95% confidence interval: 29.3–33.1). Multivariate Cox regression analysis identified smoking status, Eastern Cooperative Oncology Group performance status, and EGFR mutation subtype as independent prognostic factors for OS. Notably, patients who initiated treatment at 40 mg but de-escalated to <40 mg had the longest median TTF and OS. In terms of safety, the highest incidence of adverse events was observed in this group, followed by those who started and remained at <40 mg. Conclusion: In this real-world cohort, flexible afatinib dosing—either by initiating at 40 mg followed by dose reduction or starting at <40 mg with later escalation—was associated with favorable survival outcomes and manageable tolerability. These findings support the use of individualized afatinib dosing strategies to optimize both efficacy and safety in patients with EGFR-mutant NSCLC.