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Rare Drivers Emerge as Successful Targets in NSCLC

Caroline Seymour
Published: Friday, Jan 04, 2019

Dr Alexander Drilon

Alexander Drilon, MD
Although rare, alterations in MET, RET, and NTRK are showing significant responses to investigational targeted therapies, several of which have already been granted FDA approval or are on track to receive it, explained Alexander E. Drilon, MD.

on Advanced Non–Small Cell Lung Cancer, Drilon, a medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, discussed the emerging targetable biomarkers in NSCLC and the investigational therapies designed to target them.

OncLive: Beyond EGFR, ALK, and ROS1, what other biomarkers are emerging in the NSCLC space?

Drilon: Several other biomarkers are paired to match targeted therapies. The first group are the MET exon 14 alterations; these are found in about 4% of patients with NSCLC and have a frequency that is very similar to ALK in some series. These mutations result in activation of the MET pathway, and fortunately, they’re amenable to targeted therapy with MET inhibitors. Several MET inhibitors were in development when we detected these exon 14 alterations in clinical samples, so trials evolved very rapidly. Now, we have data on crizotinib, capmatinib, and tepotinib; capmatinib and tepotinib are selective inhibitors, whereas crizotinib is a multikinase inhibitor. Across the board, the response rates are about 30%; these rates are not quite what we’re used to seeing for EGFR, ALK, ROS1, and BRAF combination therapies.
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