Stage IV MET exon 14 NSCLC: savolitinib response complicated by recurrent drug-induced liver injury

What happened, in summary

This 73-year-old man was diagnosed on April 18, 2023, with Stage IV non-small cell lung cancer carrying a MET exon 14 skipping mutation. CT showed a 68 × 56 mm mass in the right lower lung. He had symptoms including dry cough, chest tightness and pain, difficulty breathing, low-grade fever, night sweats, hoarseness, palpitations, and other discomfort. Before targeted therapy, his liver tests were normal. On April 28, 2023, he started oral savolitinib 400 mg daily because his weight was under 50 kg. He developed back pain and leg discomfort and reduced the dose himself to 300 mg daily on day 20. On day 32, blood tests showed severe liver injury, with ALT 2822 U/L, AST 1994 U/L, alkaline phosphatase 287 U/L, and elevated bilirubin. Viral, autoimmune, imaging, and tumor-marker evaluations did not show another cause. Savolitinib was stopped, and he received hepatoprotective treatment with magnesium isoglycyrrhizinate, S-adenosylmethionine, and glutathione. Liver function returned close to normal after 2 weeks, and CT already showed tumor shrinkage. Because the cancer had responded strongly, he restarted savolitinib at 200 mg daily with glutathione, but severe liver injury recurred within 1 week. After another recovery period, he restarted savolitinib at 100 mg daily with glutathione and polyene phosphatidylcholine. Follow-up CT showed partial response and then stable disease, with no liver-function deterioration at later visits. As of June 2024, he remained on low-dose savolitinib with liver-protective medication. The case centered on balancing effective MET inhibition with recurrent liver toxicity rather than abandoning targeted therapy entirely.