Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non-Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI

LM is a rare but fatal clinical condition with a short survival time. The incidence of LM from EGFRm NSCLC has increased due to the limited efficacy of first- or second-generation EGFR TKIs in the CNS. Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean OS from LM diagnosis was 14.7 months (95% CI, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.