Clinical Outcomes of Patients with Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis in the Modern Target Therapy Era

World Neurosurg. 2023 Feb:170:e500-e509. doi: 10.1016/j.wneu.2022.11.050. Epub 2022 Nov 14.

Abstract

Background: Leptomeningeal metastasis (LM) is a severe complication in patients with non-small-cell lung cancer (NSCLC) and the optimal treatment strategy remains a challenge. This study aimed to investigate the treatment strategies and clinical outcomes in these patients.

Methods: We retrospectively reviewed the data of 44 patients with epidermal growth factor receptor (EGFR)-mutated NSCLC with LM between 2014 and 2020 at our institute. The patient characteristics, treatment approaches, LM progression-free survival (LMPFS) and overall survival (OS) after the diagnosis of LM (OSLM) were analyzed.

Results: The median OSLM was 16.0 months and the 3-year OS rate was 22.5%. The PFSLM in EGFR T790M-positive NSCLC patients with leptomeingeal disease was significantly improved by initiation of third-generation tyrosine kinase inhibitors (TKIs) compared with that of patients who were T790M negative (14.0 vs. 7.0 months; P = 0.030). A significantly higher LM disease control rate was shown in patients who received third-generation TKIs compared with previous generations of TKIs (90.1% vs. 60.0%; P = 0.024). Better Eastern Cooperative Oncology Group performance status, EGFR exon 19del, and clinical improvement of LM after therapy were independently associated with better OS.

Conclusions: The survival of patients with NSCLC with LM has improved in the target therapy era. Our study provided real-world clinical evidence that patients with EGFR-mutated NSCLC who developed LM from previous TKIs can be benefit from third-generation EGFR-TKIs, especially for patients with EGFR T790M-positive.

Keywords: EGFR mutation; Epidermal growth factor receptor tyrosine kinase inhibitor; Leptomeningeal metastasis; NSCLC; Survival outcome.

MeSH terms

  • Antineoplastic Agents*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Meningeal Carcinomatosis* / drug therapy
  • Meningeal Carcinomatosis* / genetics
  • Mutation / genetics
  • Protein Kinase Inhibitors
  • Retrospective Studies

Substances

  • ErbB Receptors
  • Antineoplastic Agents
  • Protein Kinase Inhibitors