Savolitinib in brain and leptomeningeal metastases from non-small cell lung cancer: a case report

In the population with non-small cell lung cancer (NSCLC), the incidence of mesenchymal-epithelial transition factor exon 14 (METex14) skipping mutations is approximately 3%-4%. However, the prevalence of this mutation appears to be lower among patients with NSCLC presenting with brain metastases (BMs) or leptomeningeal metastases (LMs). Although METex14 skipping mutations confer high sensitivity to small-molecule MET tyrosine kinase inhibitor (TKI), data regarding their efficacy specifically against BM or LM remain limited. Herein, we presented the case of a 66-year-old man diagnosed with lung adenocarcinoma. METex14 skipping mutations were detected in circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) via next-generation sequencing (NGS). The patient derived significant clinical benefit from savolitinib treatment, achieving an intracranial partial response (PR) upon evaluation. In conclusion, NGS-based detection of ctDNA in CSF provides a valuable tool for elucidating tumor heterogeneity and the distinct molecular profiles of central nervous system (CNS) metastases compared to primary tumors. Furthermore, savolitinib demonstrated promising intracranial activity and a manageable safety profile in this METex14-altered NSCLC case. These findings suggest that savolitinib may represent a viable novel treatment option for this patient population. Collectively, our data indicate that savolitinib holds promise as a novel treatment strategy for this population.