Journal Article

Influence of afatinib dose on outcomes of advanced EGFR-mutant NSCLC patients with brain metastases

Tan, Eng Huat, Tan, Wan-Ling, Kanesvaran, Ravindran, Toh, Chee Keong, Lim, Cindy, Lim, Darren Wan-Teck, Tan, Daniel S. W., Ang, Mei-Kim, Ng, Quan Sing, Jain, Amit

2018

Overview

Background Afatinib is an oral irreversible epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) indicated in first-line treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). Dose dependent side effects can limit drug exposure, which may impact on extracranial and central nervous system (CNS) disease control. Methods We performed a retrospective study of 125 patients diagnosed with advanced EGFRm+ NSCLC treated with first-line afatinib at a tertiary Asian cancer center, exploring clinicopathological factors that may influence survival outcomes. Median progression free survival (PFS) was estimated using the Kaplan-Meier method. Comparison of PFS between subgroups of patients was done using log-rank tests and Cox proportional hazards models. Results Out of 125 patients, 62 (49.6%) started on 40 mg once daily (OD) afatinib, 61 (48.8%) on 30 mg OD and 1 (0.8%) on 20 mg OD. After median follow-up of 13.8 months from afatinib initiation, the observed response rate was 70.4% and median PFS 11.9 months (95% CI 10.3–19.3). 42 (33.6%) patients had baseline brain metastases (BM) and PFS of those who started on 40 mg OD ( n  = 17) vs. 30 mg OD ( n  = 25) was 13.3 months vs. 5.3 months (HR 0.39, 95% CI 0.15–0.99). BM+ patients who started on 40 mg had similar PFS to patients with no BM (13.3 months vs. 15.0 months; HR 0.79, 95% CI 0.34–1.80). Conclusion In patients with advanced EGFRm+ NSCLC with BM+, initiating patients on afatinib 40 mg OD was associated with improved PFS compared to 30 mg OD, underscoring the potential importance of dose intensity in control of CNS disease.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Afatinib / Biomedical and Life Sciences / Biomedicine / Brain cancer / Brain metastases / Brain research / Cancer metastasis / Cancer Research / Central nervous system / Complications and side effects / Disease control / Dosage and administration / Dose / Drug dosages / Drug therapy / EGFR mutation NSCLC / Enzyme inhibitors / Epidermal growth factor / Epidermal growth factor receptors / Health Promotion and Disease Prevention / Health risk assessment / Lung cancer / Medical and radiation oncology / Medical imaging / Medicine/Public Health / Metastases / Metastasis / Metastatic / Mutation / NMR / Non-small cell lung cancer / Non-small cell lung carcinoma / Nuclear magnetic resonance / Oncology / Patient outcomes / Patients / Research Article / Response rates / Studies / Surgical Oncology / Tumors / Yang, Cindy