MET exon 14 skipping lung adenocarcinoma: sequential MET-TKI toxicity and ongoing chemotherapy

What happened, in summary

This 72-year-old Japanese man had atrial fibrillation and hypertension when he was treated for lung adenocarcinoma in March 2022. He underwent right upper lobectomy with systematic mediastinal and hilar lymph-node dissection. The tumor was Stage IIA, pT2aN0M0. Molecular testing after surgery found a MET exon 14 skipping mutation, while EGFR, ALK, and ROS1 were negative. PD-L1 tumor proportion score was 10%. He began adjuvant oral tegafur-uracil, planned for 2 years. In January 2024, routine imaging showed pleural dissemination, so adjuvant therapy was stopped and tepotinib 500 mg/day was started. Two months later, he developed fatigue, dyspnea, and diffuse ground-glass opacities, consistent with grade 3 interstitial lung disease. He improved with methylprednisolone pulse therapy, then oral prednisolone and tacrolimus. After recovery, he received carboplatin plus pemetrexed, followed by pembrolizumab-containing therapy and pembrolizumab monotherapy. In October 2024, worsening pleural effusion and dyspnea showed disease progression. Capmatinib was tried in November 2024 but stopped after 10 days because of high fever, oral ulcers, and new ground-glass opacities concerning for possible grade 1 interstitial lung disease. Docetaxel plus ramucirumab from December 2024 to April 2025 brought temporary control. Gumarontinib was started in May 2025, paused for grade 2 liver toxicity, restarted at a lower dose, and later stopped in August 2025 because of renal dysfunction and edema. At the time described, he was living with recurrent pleural disease and was receiving ongoing carboplatin, pemetrexed, and bevacizumab. His course showed the challenge of MET-targeted rechallenge: severe ILD did not recur, but fever, mucositis, liver injury, renal dysfunction, edema, and recurrent pleural effusion repeatedly limited treatment duration.