Addressing Clinical Questions in MET Fusion Positive NSCLC

Yonina R. Murciano-Goroff, MD, MSc, DPhil, addresses remaining clinical questions for the treatment of MET fusion positive patients with non–small cell lung cancer (NSCLC).

According to Murciano-Goroff, a medical oncologist at Memorial Sloan Kettering Cancer center, clinicians know more about MET alterations and amplifications’ impact in NSCLC and need to expand on their knowledge from there to MET fusion tumors. Moreover, they have tried to translate this data into treatment for patients with MET fusion positive tumors.

One identified MET fusion included the MET G1090A resistance mutation, which drives resistance to type 1 MET tyrosine kinase inhibitors, such as crizotinib (Xalkori). Researchers identified this using serial targeted genomic sequencing, and analyzed the activity of MET inhibitors with alternative binding modes, and structural modeling in vitro kinase assays.

Results of the analysis showed that switching the type 2 MET inhibitors after the patient developed resistance to the type 1 inhibitors helped overcome treatment. However, these were results from a pre-clinical study that shows how far the field still needs to go.

Transcription:

0:08 | I would say that there's still a lot of open questions [regarding MET fusion positive patient’s lung cancer], which makes it an important area. As a field, we are still working out what is the optimal approach for our patients with MET fusion positive disease. And what I would say is that most of what we have been doing to date, in terms of the targeted therapy front, has really been trying to translate results from other [treatments for] MET positive tumors.

0:38 | So we know that exon 14 skipping alterations in NSCLC, we know MET amplifications even in NSCLC better than we know MET fusions. So then trying to translate from those cases from what we know about what works in patients with other MET alterations to MET fusions has kind of been the strategy to date.