Significant benefit of high-dose furmonertinib in the treatment of leptomeningeal metastases from non-small-cell lung cancer with EGFR ex19Del mutation: Two case reports and a literature review

Abstract

Abstract Background: Leptomeningeal metastases (LMs) are a devastating metastatic complication of non-small-cell lung cancer (NSCLC). There is no standard treatment for epidermal growth factor receptor (EGFR) mutant NSCLC, and improving the clinical prognosis for patients with LMs has become an urgent problem in clinical treatment. Preclinical data suggest that third-generation epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) have greater blood-brain barrier penetration than first- and second-generation EGFR-TKIs and can effectively inhibit central nervous system (CNS) metastases. Furmonertinib is a potent and irreversible third-generation EGFR-TKI. The parent drug and its metabolites can be distributed to brain tissue. Case Description: Here, we report for the first time that high-dose furmonertinib is not only effective in improving neurological symptoms caused by LMs, but also prolongs the survival time of patients. Side effects were limited but manageable. Following the diagnosis of LMs, genetic testing of blood or tissue samples from both patients resulted in the EGFR ex19del mutation. The first case was a 58-year-old woman with advanced lung adenocarcinoma. Furmonertinib (240mg/day) was given as initial treatment. The patient's neurological symptoms resolved significantly after 1 month, and she achieved complete response (CR) of the intracranial lesions after 10 months. In addition, the therapeutic effect has lasted for > 13 months and remained in close follow-up. The second case was a 69-year-old woman with advanced lung adenocarcinoma. She was treated with furmonertinib (160mg/day) as initial treatment and experienced immediate relief of neurological symptoms. The CNS response lasted >14 months and partial response (PR) was achieved. As of the last follow-up, iPFS, PFS and OS were not achieved in neither patient. Conclusion: Furmonertinib may be an optional and effective management strategy for patients with NSCLC and EGFR-mutated LMs.