The Importance of Targeting RET in NSCLC

Transcript: Jessica Bauman, MD: We know that for these RET fusions, the biology of them creates a protein that is overexpressed on the surface of cancer cells that is basically constitutively active. It’s constantly on and sending signals into the cell to grow and develop. We know that this ultimately is what leads to cancer growth for oncogenic-driven cancers. We also know that targeting this specific protein with a tyrosine kinase inhibitor can shut off the signaling, and there is significant duration of response for patients with these targetable mutations.

There are several RET-fusion mutations that have been described in the literature, though the most common is KIF5B; others are NCOA4, CCDC6, TRIM33. Although this, in my mind, is sort of an alphabet soup, the most important one to know is KIF5B. It is the most common, anywhere between 70% and 90% of cases. Though what we have started to see, as we see more of these drugs in development, is that sometimes 1 fusion partner may respond better than another fusion partner. It’s important to know that there are different types but that certainly, many of these fusion partners have seen significant responses.

As many people know, when they’re treating people with lung cancer, we used to really treat everybody in the same way. We gave them platinum doublet chemotherapy, and they had similar survival. Over the course of the last 20 years, we have divided patients with non—small cell lung cancer into 2 different subcategories. In particular, people with adenocarcinoma are found to have what we call oncogenic-driver mutations. The first of these that was really recognized and developed were patients with EGFR mutations.

But we’ve also seen this now for patients with ALK mutations, for ROS1 mutations, for BRAF mutations. As we recognize all these different genetic alterations in mutations, we are able to personalize the repeat for each individual patient based on what their underlying genetics of their tumor are. And for RET, although there have been some targeted treatments over the course of the last many years that have been tried, it is only recently that we’ve seen development of very specific RET inhibitors that are allowing us to potentially offer something new to this patient population.

Transcript Edited for Clarity