Safety and Synergy of Capmatinib Plus Stereotactic Radiotherapy in MET Exon 14-Mutated Non-Small Cell Lung Cancer: A...

MET exon 14 skipping mutations define a rare subset of non-small cell lung cancer (NSCLC). Capmatinib, a selective MET inhibitor, has shown efficacy, but oligometastatic lesions often require local therapy. Data on combining capmatinib with stereotactic body radiotherapy (SBRT) remain limited. A 73-year-old man with well-controlled type 2 diabetes and a history of smoking presented with a right upper lobe mass, mediastinal lymphadenopathy, vertebral metastases, and a small brain lesion. Biopsy confirmed adenocarcinoma (thyroid transcription factor-1 (TTF-1) +, Programmed Death-Ligand 1 (PD-L1) >80%), and next-generation sequencing revealed a MET exon 14 skipping mutation. He received capmatinib (800 mg/day) and denosumab, with SBRT to vertebral metastases and later to the primary lung tumor. Capmatinib was held five days before and resumed five days after each SBRT course. Treatment was well tolerated with no significant toxicity. Imaging showed durable regression of primary and metastatic lesions, with complete resolution of the brain lesion and successful control of isolated oligoprogression. At 24 months, the patient remains alive with no evidence of disease progression. The combination of capmatinib and SBRT was safe and effective, achieving local and systemic tumor control. Temporary suspension of capmatinib during SBRT, along with careful monitoring, optimized tolerability, and outcomes. This case supports the feasibility and potential synergy of precision multimodal therapy in MET-driven oligometastatic NSCLC, highlighting the need for further prospective studies.