MET Y1003N-Mutant Lung Adenocarcinoma Responding to Tepotinib

What happened, in summary

A 63-year-old woman who had never smoked was diagnosed with Stage IV lung adenocarcinoma after imaging showed a left upper-lung mass, pleural fluid, and bone metastases in the spine and sacrum. She began treatment with cisplatin, pemetrexed, and pembrolizumab. Molecular testing later found a rare MET Y1003N mutation.

After the first treatment stopped controlling the cancer, she received several additional chemotherapy regimens. Capmatinib, a MET-targeted drug, was tried as fifth-line therapy, but it had to be stopped after only 22 days because of significant liver toxicity and low blood counts before its effectiveness could be established. More chemotherapy followed.

One year and 11 months after diagnosis, she started another MET inhibitor, tepotinib. The tumors shrank by about 31%, meeting criteria for a partial response after 5 months. She remained on tepotinib for 8 months before the cancer recurred. Vinorelbine was then tried but did not produce a meaningful response, and chemotherapy was eventually stopped.

She died about 3 years after treatment began. Her course is notable because tepotinib provided a meaningful period of tumor control despite the unusual MET mutation and the large number of treatments she had already received.