Abstract
BackgroundAfatinib 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.MethodsWe 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.ResultsOut 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).ConclusionIn 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.
Highlights
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)
Intracranial efficacy of first-line EGFR TKIs has not been established in prospective large-scale studies, clinical observations from trials support intracranial activity with afatinib – a second-generation, irreversible pan-human epidermal growth factor receptor (HER) inhibitor
Radiological assessments of patients were performed at 2–3 month intervals as decided by the treating physician, with brain imaging by either contrasted computed tomography (CT) or magnetic resonance imaging (MRI) brain performed regularly for patients with documented brain metastases
Summary
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). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for first-line treatment of advanced NSCLC with sensitizing EGFR mutations [1, 2]. Intracranial efficacy of first-line EGFR TKIs has not been established in prospective large-scale studies, clinical observations from trials support intracranial activity with afatinib – a second-generation, irreversible pan-human epidermal growth factor receptor (HER) inhibitor. Due to potent EGFR wild-type inhibition, afatinib is associated with increased skin and gastrointestinal toxicities, resulting in dose reductions reported in up to 53.3 and 28% patients in the randomized LUX-Lung 3 and 6 trials respectively [7]. The potential impact of dose reductions with afatinib on CNS disease control remains poorly characterized
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