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Capmatinib in MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma with Extensive Central Nervous System
Tae Woo Kim1, Kyung Mi Lee2, Seung Hyeun Lee1
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, South Korea.
Abstract:
Several selective mesenchymal-epithelial transition (MET) inhibitors have recently demonstrated favorable systemic efficacy in MET exon 14 skipping mutation-positive non-small cell lung cancer. However, there are limited data on their efficacy against central nervous system (CNS) metastasis, especially leptomeningeal seeding. Recently, we encountered a case of a 65-year-old woman who was diagnosed with metastatic lung adenocarcinoma. As routine molecular testing showed no genomic alterations, including epidermal growth factor receptor mutation and anaplastic lymphoma kinase translocation, the patient received a frontline platinum-doublet followed by paclitaxel. However, the tumor did not respond to these therapies, and her condition became deleterious owing to extensive brain and leptomeningeal metastases. Plasma genotyping revealed that the tumor harbored a MET exon 14 skipping mutation, and we started capmatinib, a selective MET inhibitor. The CNS lesions markedly decreased and the performance status of the patient dramatically improved. Our report highlights the significant CNS activity of capmatinib, even in cases of leptomeningeal metastasis. In addition, this report emphasizes the importance of the active utilization of molecular profiling to detect rare but druggable genetic alterations for the better management of patients with lung cancer.
Insights
Capmatinib shows significant efficacy against brain and leptomeningeal metastases in lung cancer with MET exon 14 skipping mutations. This highlights the importance of molecular profiling for targeted therapy in advanced lung cancer.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations (METex14) shows response to MET inhibitors.
- Limited data exist on the efficacy of MET inhibitors against central nervous system (CNS) metastases, particularly leptomeningeal disease, in NSCLC.
Observation:
- A 65-year-old woman with metastatic lung adenocarcinoma and extensive CNS/leptomeningeal metastases, initially negative for common driver mutations, received standard chemotherapy without response.
- Plasma genotyping identified a MET exon 14 skipping mutation, leading to treatment with capmatinib, a selective MET inhibitor.
Findings:
- Capmatinib treatment resulted in marked reduction of CNS lesions and significant improvement in the patient's performance status.
- The patient experienced substantial clinical benefit despite widespread leptomeningeal metastasis.
Implications:
- Capmatinib demonstrates significant CNS activity, including in leptomeningeal metastasis, for METex14 NSCLC.
- Molecular profiling is crucial for identifying rare, actionable mutations like METex14, enabling targeted therapies for improved lung cancer patient management.
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