Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer

Abstract

Introduction: Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC.

Methods: Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November 2017 were analyzed retrospectively. They received gefitinib, erlotinib, or afatinib until disease progression, death, or intolerable adverse events. The cumulative incidence of subsequent BM of initial non-BM patients, progression-free survival (PFS), and overall survival (OS) of the BM and non-BM patients were estimated and compared using the Kaplan-Meier and log-rank tests.

Results: 306 NSCLC patients were enrolled, with 116, 75, and 115 receiving first-line gefitinib, erlotinib, and afatinib, respectively. The afatinib group had a better PFS [12.7 versus 9.8 months; hazard ratio (HR) 0.59, p = 0.001] and OS (39.1 versus 22.0 months; HR 0.64, p = 0.035) than the gefitinib group. Afatinib tended to provide better BM prevention than gefitinib (BM cumulative incidence, HR 0.49; 95% confidence interval 0.34-0.71, p < 0.001) according to a Cox model adjusted for possible confounders. Patients with initial BM had a shorter PFS (p < 0.001) and OS (p = 0.015) than those without initial BM. Among the former, there were no differences in median PFS (p = 0.34) and median OS (p = 0.46) in the three EGFR-TKI groups.

Conclusions: Our data suggested that, compared with gefitinib, afatinib provided better benefits significantly in terms of PFS and OS. Both had the same effectiveness in preventing subsequent BM.

Keywords: EGFR mutation; brain metastasis; non-small cell lung cancer; tyrosine kinase inhibitor.

Figure 1.

Flow chart describing enrollment of patients in the study. EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

Figure 2.

Progression-free survival (a) and overall survival (b) in patients with non-small cell lung cancer and epidermal growth factor receptor gene mutations treated with gefitinib, erlotinib, or afatinib. CI, confidence interval; NR, not reached.

Figure 3.

The prevention and treatment for brain metastases by three first-line epidermal growth factor receptor–tyrosine kinase inhibitors in patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer. Cumulative incidence (a) of subsequent BM in patients without prior CNS involvement treated with gefitinib, erlotinib, or afatinib. Progression-free survival (b) and overall survival (c) of all patients with EGFR mutation-positive advanced non-small cell lung cancer and brain metastases. Progression-free survival (d) and overall survival (e) in patients with EGFR mutation-positive advanced non-small cell lung cancer and BM treated with gefitinib, erlotinib, or afatinib. BM, brain metastases; CNS, central nervous system; EGFR, epidermal growth factor receptor; NR, not reached.