An Observational Study of Afatinib 30 mg Daily in Patients With Advanced Non‐Small‐Cell Lung Cancer Harboring Common
EGFR
Mutations Treated With Afatinib
Kenneth Sooi, Pongwut Danchaivijtr, C. K. Wong, V. D. Tu, Manavi Sachdeva, B. C. Tai, Ross A. Soo ABSTRACT
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;