MET gala.

Last week we heard all about the efficacy of RET-inhibitors for the subset of non-small cell lung cancer (NSCLC) patients with RET-activating mutations. Similar to RET, MET driver mutations are also often exclusive of other driver mutations, and they are associated with poor prognosis. In the phase 2 GEOMETRY mono-1 trial, over 350 patients with advanced NSCLC with MET aberrations received the highly-selective MET inhibitor capmatinib. Among these, just over 25% had exon 14 skipping mutations (more likely to be female non-smokers) while the rest had MET amplification. Capmatinib appeared most effective among the former group with an overall response rate of 68% for treatment-naive patients (median duration 13 months) and 41% for those with prior treatment (median duration 10 months). Among the latter group, capmatinib response rate heavily depended on the extent of MET amplification (i.e. lower amplification was likely a bystander rather than driver). TBL: The majority of patients with NSCLC and MET exon 14 skipping mutations have durable responses to MET-targeted therapy with capmatinib. | Wolf, N Engl J Med 2020


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