Joshua Bauml, MD of the University of Pennsylvania discusses MET Exon 14 Skipping Mutations and Crizotinib. This is an important genetic operation. These mutations ensure less degradation of MET on the cell surface. With this, they will have more activity. Now, crizotinib, which is already FDA approved and we know as an ALK inhibitor is actually a MET inhibitor.
MET inhibition with crizotonib and cabozantinib has been found to have significant activity. MET Exon 14 Skipping mutations can be seen in two populations older adenocarcinoma patients (never or light smokers) and those with pleomorphic carcinoma or sarcomatoid carcinoma. The latter tend to have a very poor response rate to cytotoxic chemotherapy and have poor prognosis. And, it was found that 20-30% of these patients have MET Exon 14 skipping mutations.
Lastly, Dr. Bauml reminds that when evaluating these patients, it is very important to do a next generation sequencing assay on them.