31 An animal model of intrathecal bevacizumab for LM provided safety data to allow the use of bevacizumab in people with treatment\refractory LM in phase I/II studies in the category. LM was diagnosed, 12 (85.7%) patients had clinical symptoms, 71.4% (10/14) of patients were diagnosed with LM by cytology, and five (35.7%) patients had a performance status (PS) score? ?2. The median LM PFS was 9.3 months (95% CI: 8.2C10.4), and the LM ORR was 50%. The safety findings AN7973 in the present study were consistent with the known profile of osimertinib with bevacizumab; the median LM OS was 12.6 months, and the one\year survival rate was 35.7%. Conclusions Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC. Key points Significant findings of the study To date, there is no prospective clinical study on the treatment of osimertinib combined with bevacizumab in EGFRm NSCLC with LM. What this study adds The median LM PFS was 9.3 months (95% CI: 8.2C10.4), and the LM ORR was 50%, the median LM OS was 12.6 months, and the one\year survival rate was 35.7%. Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC. mutation, leptomeningeal metastasis, non\small cell lung cancer, osimertinib Abstract we evaluated the first phase II prospective clinical trial to assess the efficacy and safety of osimertinib combined with bevacizumab for LM from EGFRm NSCLC. Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC. Introduction Lung cancer remains AN7973 a leading cause of death worldwide, and most cases of non\small cell lung cancer (NSCLC) are diagnosed at an advanced stage. 1 Leptomeningeal metastasis (LM) is a fatal complication of advanced NSCLC associated with poor prognosis and rapid deterioration of performance status. 2 , 3 The incidence of LM is increasing, reaching 3.8% in molecularly unselected NSCLC patients, AN7973 being more frequent in the adenocarcinoma subtype and occurring in up to 9.4% in epidermal growth factor receptor mutation (EGFRm) lung cancer patients; one\third of patients have concomitant brain metastasis. 4 , 5 , 6 , 7 This increased incidence may in part be conducive to the increased survival of patients with EGFRm advanced NSCLC since the introduction of EGFR\tyrosine kinase inhibitors (TKIs). 8 Currently, no standard therapeutic regimen for LM with EGFRm NSCLC has been established because of its rarity and heterogeneity. 9 TKIs are the AN7973 first\line treatment of choice for patients with EGFRm NSCLC. The leptomeningeal space is a sanctuary site for tumor cells and therapeutic agents due to the presence of an active blood\brain barrier (BBB). 10 Therefore, CSF concentration is an important factor affecting the treatment of LM with TKIs. 9 , 11 , 12 Standard dose first\ and second\generation EGFR\TKIs have good systemic efficacy but suboptimal central nervous system (CNS) penetration, as evidenced by preclinical studies of brain distribution and clinical reports of CSF penetration. 13 Osimertinib is a third\generation irreversible, oral EGFR\TKI that potently and selectively inhibits both EGFR\TKI sensitizing and EGFR T790M resistance mutations that has demonstrated efficacy in NSCLC CNS metastasis. 14 , 15 , 16 , 17 , 18 , 19 Preclinical, phase I/II clinical studies Col18a1 and the AURA program (AURA extension, AURA2, AURA17 and AURA3) have shown that osimertinib has higher brain permeability than first\ and second\generation treatment. 13 , 20 Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), and animal studies and autopsy specimens have shown that VEGF plays an important role in LM. 21 VEGF and EGFR share many overlapping and parallel downstream pathways. 22 Biological rationale shows that the inhibition of the EGFR and VEGR signaling pathways could improve the efficacy of antitumor therapy and remove the resistance AN7973 of EGFR inhibition..