Osimertinib With or Without Bevacizumab for EGFR- Mutant Non-small Cell Lung Cancer With Leptomeningeal Metastasis

Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib is an oral,third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations .AURA I/II study and other preclinical study suggested that Osimertinib exhibited a better blood-brain barrier(BBB) penetration than the other EGFR-TKIs (gefitinib, erlotinib, or afatinib).The BLOOM 、AURA and FLURA study demonstrated that osimertinib showed encouraging activity and manageable tolerability in pretreated EGFR-mutant NSCLC patients with LM. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF). Animal study and autopsy specimens showed that VEGF is an essential factor in LM. Recently study showed EGFR-TKIs plus bevacizumab prolonged PFS and OS in patients with EGFR-mutant NSCLC and multiple brain mteastasis when compared with EGFR-TKIs alone. Howerver osimertinib combined with bevacizumab could benefit patients with LM from EGFR- mutant NSCLC remains undetermined. Therefore, the purpose of the study is to evaluate the safety and efficacy of osimertinib combined with bevacizumab for EGFR- mutant non-small cell lung cancer with leptomeningeal metastasis