Treatment of third-generation EGFR-TKIs resistant lung cancer with leptomeningeal metastasis using intraventricular chemotherapy combined with doubled dose of famotinib and bevacizumab monoclonal antibody
Objective To assess the efficacy and safety of intraventricular chemotherapy and double dose of furmonertinib with or without bevacizumab,in treating leptomeningeal metastasis(LM)from non-small cell lung cancer(NSCLC)resist-ant to third-generation epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)targeted therapies.Methods The study retrospectively included 68 NSCLC-LM patients who developed resistance after third-generation EG-FR-TKIs at the Affiliated Brain Hospital of Nanjing Medical University from September 1,2021 to May 31,2023.40 pa-tients received intraventricular chemotherapy(30 mg or 50 mg pemetrexed)and double dose of furmonertinib(160 mg o-rally daily)combined with bevacizumab in the observation group,and 28 patients in the control group received only intra-ventricular chemotherapy and double dose of furmonertinib.Response Assessment in Neuro-Oncology(RANO)were used to evaluate the assessment of LM response.All adverse events were recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events,version 5.0.Clinical outcomes were compared with the Kap-lan-Meier log-rank test.Results Based on RANO criteria,30(44.1％)patients had responsive disease and 31(45.6％)patientshad stable disease,seven patients(10.3％)developed progressive disease.The observation group had 20(50.0％)responsive disease,18(45.0％)stable disease and 2(5.0％)progressive disease,while the control group had 10(35.7％)responsive disease,13(46.4％)stable disease and 5(17.9％)progressive disease.However,there was no sta-tistically significant difference in the effective rate between the two groups,x2=3.414,P=0.181.Enhanced MRI showed improvement in 32(47.1％)patients,stability in 30(44.1％)patients,and progression in 6(8.8％)patients.The median intracranial progression-free survival(iPFS)in the entire group was 7.6 months,and the median iPFS was 4.6 and 11.6 months,respectively in the control and observation groups(HR=2.724,95％CI:1.425-5.207,x2=10.003,P=0.002).The median overall survival(OS)in the control group was 8.8 months,the observation group was not reached(HR=4.391,95％CI:1.606-12.001,x2=9.930,P=0.002).The most common adverse events of 160 mg furmonertinib were rash and diarrhea,the common side effects of bevacizumab included bleeding and proteinuria,and my-elosuppression and aseptic meningitis were the main adverse reactions of intraventricular chemotherapy.There was no sta-tistical difference between the two groups.Conclusion Intraventricular chemotherapy and double dose of furmonertinib combined with bevacizumab can improve the quality of life and prolong the survival time in NSCLC patients with LM,with a manageable safety profile.
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