Application Of Osimertinib In EGFR-mutant Non-small Cell Lung Cancer With Leptomeningeal Metastases

Objective: Evaluating the efficacy and safety of osimertinib in patients with EGFR-mutant non-small cell lung cancer and leptomeningeal metastases.Methods: The clinical data of patients with EGFR-mutant non-small cell lung cancer patients and leptomeningeal metastases treated with osimertinib were retrospectively analyzed to evaluate the efficacy and safety of osimertinib.Results: We analyzed 12 EGFR-mutant non-small cell lung cancer patients who were treated with osimertinib after leptomeningeal metastasis,including 5 males and 7 females,with a median age of 54(46-62)years.All patients except one who had primary T790 M mutation received first-generation EGFR-TKI treatment and progressed.Before treatment with osimertinib,EGFR mutation was detected again in 8 patients,of which 3 patients(37.5%)harbored T790 M mutation.The median Karnofsky Performance Scores(KPS)of 12 patients before therapy was 70(60-80),and after therapy the median KPS was 90(60-100),the difference was statistically significant(Z=-2.754,P=0.006).Based on the evaluation of neurological symptoms,cerebrospinal fluid cytology,neuroimaging and primary tumors in 12 patients,Efficacy were observed in 10 patients,of which 100%(3/3)were T790 M positive,and the median time of clinical responses was 20(7-28)days.The median progression-free survival of all patients was 8.1 months.The clinical response rate of high dose(160 mg)osimertinib was 100%,but the degree of adverse events with high dose(160 mg)were higher than conventional dose(80 mg): average category(2.4vs1.3),average grade(1.4vs1.1).After the progression of the treatment with the initial dose of osimertinib,one patient achieved response again by increasing the dose of osimertinib,and the average survival time of 6 patients who continued the original treatment was 6.4 months.Conclusion: Regardless of the state of T790 M mutation,osimertinib has significant and rapid intracranial and extracranial therapeutic effects on EGFR-mutant NSCLC with LM resistant to the first generation EGFR-TKI,and may be more suitable for T790 M positive patients.The toxic reaction of 160 mg osimertinib is significantly may be higher than that of 80 mg,but it may be more effective in the treatment of central nervous system diseases,and there is hope for the treatment of advanced diseases with standard dose of osimertinib.The use of Osimertinib in EGFR-mutant NSCLC with LM may still benefit from continued treatment after progression.