An Observational Study of Afatinib 30 mg Daily in Patients With Advanced Non‐Small‐Cell Lung Cancer Harboring Common <scp>EGFR</scp> Mutations Treated With Afatinib

BACKGROUND: Afatinib is an approved first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring sensitizing EGFR mutations. At the standard 40 mg dose, 28%-53% of patients in randomized trials required dose reductions due to adverse events (AEs), predominantly cutaneous and gastrointestinal. This study evaluated whether a 30 mg starting dose could improve tolerability without compromising efficacy. METHODS: This multicenter, single-arm phase 2 study enrolled treatment-naive patients with advanced EGFR-mutant NSCLC. Patients received afatinib 30 mg daily until progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. Using A'Hern's single-stage design (one-sided α = 0.1, 80% power), 62 patients were required to distinguish a target 6-month of PFS ≥ 75% from ≤ 62%. RESULTS: The study was terminated early due to slow accrual; 30 patients were enrolled between May 2023 and May 2024. Median follow-up was 11.3 months (IQR 9.6-15.5). The 6-month PFS rate was 93.2% (95% CI 75.5-98.3), median PFS of 15.8 months (95% CI 13.4-not reached) and median TTF of 17.0 months. ORR was 80% and DCR 96.7%. Common treatment-related AEs included diarrhea (83.3%), mucositis (60.0%), paronychia (60.0%), and acneiform rash (46.7%). Grade ≥ 3 AEs occurred in 10.0% of patients, with no Grade 4-5 events. Dose modification was required in 13.3% of patients. CONCLUSION: Afatinib 30 mg daily was well tolerated and demonstrated encouraging efficacy, with a 6-month PFS of 93.2%, suggesting outcomes comparable to standard dosing. TRIAL REGISTRATION: Registration number: NCT04909073; https://clinicaltrials.gov.