Abstract

Objectives In EGFR-mutated non-small cell lung cancer (NSCLC) patients, approximately 80-90% of leptomeningeal metastasis (LM) develops after failed initial treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI). However, the efficacy of rechallenging with previously administered EGFR-TKIs in patients with EGFR-mutated NSCLC and the LM that develops following EGFR-TKI treatment failure remains unknown. Materials and methods We retrospectively reviewed medical records of patients with EGFR-mutated NSCLC and LM, from November 2011 to August 2019. The patients were classified according to the LM treatment type: switched to previously unadministered EGFR-TKIs (Switch-TKI) or rechallenge with previously administered EGFR-TKIs (Rechallenge-TKI). Results In total, 50 patients treated with EGFR-TKI after LM diagnosis were included; 35 were treated with Switch-TKI and 15 with Rechallenge-TKI. The median overall survival (OS) from the time of LM diagnosis was 6.2months in all study patients. According to the treatment type, the median OS from the time of LM diagnosis was 6.9months in Switch-TKI patients and 4.9months in Rechallenge-TKI patients. There was no significant difference in the OS between the Switch-TKI and Rechallenge-TKI groups (P = 0.864). Thirty-five patients were treated with erlotinib and 15 with osimertinib; Regardless of the type for EGFR-TKI, there was no significant difference in OS between patients treated with Switch-TKI and those treated with Rechallenge-TKI. Conclusion Rechallenge of previously administered EGFR-TKIs may be a therapeutic option for LM development after EGFR-TKI treatment failure in patients with EGFR-mutated NSCLC, not only switching to previously unadministered EGFR-TKIs.

Highlights

  • Leptomeningeal metastasis (LM) develops in 3–5% of patients with metastatic non-small cell lung cancer (NSCLC) [1,2,3], and approximately 10% of patients with epidermal growth factor receptor (EGFR)mutated NSCLC [4,5,6]

  • Thirty-five patients were treated with erlotinib and 15 with osimertinib; Regardless of the type for EGFRTKI, there was no significant difference in overall survival (OS) between patients treated with Switch-tyrosine kinase inhibitors (TKIs) and those treated with Rechallenge-TKI

  • Our findings suggest that rechallenge of previously administered EGFR-TKIs may be a therapeutic option for LM development after EGFR-TKI treatment failure in patients with EGFR-mutated NSCLC, switching to previously unadministered EGFR-TKIs

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Summary

Introduction

Leptomeningeal metastasis (LM) develops in 3–5% of patients with metastatic non-small cell lung cancer (NSCLC) [1,2,3], and approximately 10% of patients with epidermal growth factor receptor (EGFR)mutated NSCLC [4,5,6]. Several previous studies have demonstrated that patients with EGFR mutated NSCLC treated with EGFR tyrosine kinase inhibitors (TKIs) have a median survival of approximately 6 to 12 months after diagnosis of LM [1, 4, 7,8,9,10,11,12]. A previous study showed that erlotinib had a better cytologic conversion rate in the CSF than gefitinib in patients with EGFR-mutated NSCLC and LM [7, 13]. A single-arm prospective study demonstrated that the efficacy of osimertinib was superior to historical data of first- and secondgeneration EGFR-TKIs in patients with EGFR-mutated NSCLC and LM [8]

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