Abstract / Summary
MET exon 14 (METex14) skipping mutations occur in a subset of non-small cell lung cancer (NSCLC) cases, mostly affecting older patients with multiple comorbidities.Selective MET tyrosine kinase inhibitors (TKIs) capmatinib and tepotinib represent the standard of care; however, real-world management is frequently complicated by agent-specific toxicity and class-effect peripheral edema.Sequential use of MET TKIs following agent-specific intolerance and the feasibility of non-standard tepotinib dosing schedules remain poorly characterized.A 74-year-old man with diabetes mellitus, hypertension, and stage IVA METex14mutated lung adenocarcinoma (cT3N3M1a, malignant pleural effusion, KRAS p.G12V co-mutation) received three cycles of first-line pemetrexed plus carboplatin with residual active disease.Capmatinib 200 mg twice daily, initiated as biomarker-directed therapy, was discontinued after 1.5 months due to severe multi-organ toxicity, including grade 3 hyperglycemia, acute kidney injury, elevated pancreatic enzymes, hypercalcemia, and hyponatremia, with Eastern Cooperative Oncology Group (ECOG) performance status worsening from 2 to 3. Tepotinib 225 mg once daily was initiated with early clinical and biochemical improvement.Grade 3 bilateral pedal edema at two months necessitated stepwise dose-frequency modification of tepotinib together with diuretic therapy.Apparent radiological progression at 10 months was managed as suspected pseudoprogression in view of sustained clinical stability, and therapy was continued.After 13 months of tepotinib therapy, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) demonstrated complete metabolic remission in February 2024.This case shows that capmatinib intolerance does not prevent the benefit from sequential tepotinib and that adjusting the dose frequency can effectively manage MET inhibitor-associated peripheral edema without compromising oncological outcomes, achieving complete remission in an elderly comorbid patient.