Rapid tumor progression occurring after the discontinuation of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is referred to as a disease flare of non-small cell lung cancer (NSCLC). The clinicopathological features of disease flares after osimertinib discontinuation remain unclear.

We report a patient with EGFR-mutated NSCLC who experienced the progression of leptomeningeal metastases as a disease flare shortly after the discontinuation of osimertinib despite the absence of radiological or cytological findings.

If CNS symptoms develop immediately after the discontinuation of osimertinib, the possibility of a CNS disease flare should be considered even if no radiological or cytological findings are present.