Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR‐mutation non‐small cell lung cancer: A phase II single‐arm prospective clinical trial

BACKGROUND: Leptomeningeal metastasis (LM) is associated with poor prognosis in non‐small cell lung cancer (NSCLC). The aim of this study was to investigate the efficacy and safety of osimertinib combined with bevacizumab for LM from epidermal growth factor receptor mutation (EGFRm) NSCLC. METHODS: We conducted a phase II single‐arm prospective clinical trial of EGFRm NSCLC with LM treated with osimertinib combined with bevacizumab. LM response assessment was based on the modified RANO LM radiological criteria; CNS and extra‐CNS response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary end points included LM progression‐free survival (PFS) and objective response rate (ORR); the secondary end points included safety and LM overall survival (OS). RESULTS: A total of 14 patients were included in the study, with a median age of 61 years, and they were predominantly female (64%). EGFR mutations were reported in exons 19 del (n = 7) and 21 L858R (n = 7). When 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: 8.2–10.4), and the LM ORR was 50%. The safety findings 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: 8.2–10.4), 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.