Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases

Abstract

Aim: The aim of the present study was to investigate the prognostic impact of central nervous system metastases (CNS) after acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in EGFR-mutant non-small cell lung cancer (NSCLC).

Patients and methods: We defined CNS-collapse as death due to uncontrolled and progressive CNS metastases. Post-progression survival (PPS) after initial TKI failure and T790M status were retrospectively compared in 92 patients with or without CNS collapse.

Results: The median PPS in 32 patients with CNS-collapse (16.7 months) was significantly shorter than that of 60 without (26.8 months) (p=0.0002). T790M was detected in four (12%) out of the 32 CNS-collapse patients and in 26 (43%) out of 60 without (p=0.0026). Median PPS in 39 patients with leptomeningeal metastases (LM) (11.4 months) was significantly shorter versus 53 without (26.8 months) (p=0.0006). The median PPS was 25.1 months in 40 patients with brain metastases and 11.2 months in 52 without (p=0.0387). T790M was detected in 4/5 resected brain tumors (80%) and in 1/26 cerebrospinal fluid (CSF) samples (4%) (p=0.0008).

Conclusion: CNS-collapse represented poorer prognosis, which was associated with T790M-negative status and LM. Controlling CNS metastases, especially LM, is important to achieve longer survival.

Keywords: Central nervous system; T790M; acquired resistance; brain metastases; epidermal growth factor receptor-tyrosine kinase inhibitor; leptomeningeal metastases.