RET-Fusion NSCLC Treatments LOXO-292 & BLU-667

Transcript:Mark A. Socinski, MD: One of the more exciting data subsets we’ve seen between the American Association for Cancer Research [AACR] and the American Society of Clinical Oncology [ASCO] is regarding RET fusion. We’ve been testing for RET fusion, but we had drugs like cabozantinib [Cometriq], sunitinib [Sutent], and vandetanib [Caprelsa] that had some RET activity, but they had more activity in other kinases. The 2 drugs—LOXO-292 and BLU-667—are pretty impressive RET inhibitors.

Thomas E. Stinchcombe, MD: The drugs that we’re looking for were really multitargeted kinases. Many patients need a dose reduction to do the EGFR and VEGF toxicities. We’re always concerned hitting RET with the potency that you need to change the disease, correct?

Both the BLU-667 and the LOXO-292 drugs are much more specific as potent RET inhibitors, and that’s going to be a huge advantage. The LOXO drug at ASCO had an overall response rate of around 77%, with very minimal grade 3 or 4 toxicities.

Mark A. Socinski, MD: Almost 0.

Thomas E. Stinchcombe, MD: Their DLT [dose-limiting toxicity] was tumor lysis syndrome; that’s the DLT you want, especially in solid tumor oncology—we rarely see that problem. So that’s very promising. And the BLU-667 drug has a very similar profile; the data are a little bit less mature, but I think it’s going to have very similar activity, so we may have 2 drugs for this patient population that we have struggled with previously.

Mark A. Socinski, MD: It really has heightened enthusiasm. Getting back to my point of broad molecular testing, you’re not going to find RET fusions very often. Again, you have to think about the HER2 and MET amplification and mutation.

Thomas E. Stinchcombe, MD: The challenge is that a lot of us use our internal panels of 50 genes, which are quickly becoming antiquated as we identify more subsets that are MET—exon 14 skipping, which is in about 3% of patients. When you see tumor lysis, you have an active drug that you’re going to want to clear with patients who have RET fusions in lung cancer because they are very active drugs in this setting.

Thomas E. Stinchcombe, MD: And they have central nervous system activity.

Transcript Edited for Clarity