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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

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

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

Published in: BMC Cancer | Issue 1/2018

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Abstract

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.
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Metadata
Title
Influence of afatinib dose on outcomes of advanced EGFR-mutant NSCLC patients with brain metastases
Authors
Wan-Ling Tan
Quan Sing Ng
Cindy Lim
Eng Huat Tan
Chee Keong Toh
Mei-Kim Ang
Ravindran Kanesvaran
Amit Jain
Daniel S. W. Tan
Darren Wan-Teck Lim
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-5110-2

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