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

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 ap-proaches, 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 signifi-cantly 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 perfor-mance 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.

Automated summary

This study investigated treatment strategies and clinical outcomes in patients with non-small-cell lung cancer (NSCLC) and leptomeningeal metastasis (LM). The findings showed that the use of third-generation tyrosine kinase inhibitors (TKIs) significantly improved LM progression-free survival (LMPFS) and overall survival (OS) in NSCLC patients with EGFR T790M mutation. Better Eastern Cooperative Oncology Group performance status, EGFR exon 19del, and clinical improvement of LM after therapy were independently associated with better OS.