GIST Mutations: Are Some Worse Than Others?

Shreyaskumar Patel, MD: A question that I’m going to pose to you, from an educational perspective, is that the mutations come in various flavors if you will, so there are point mutations, deletions, insertions, that sort of stuff. There are some data out there that some may be worse than others. Do you have any comments about that part?

Andrew Wagner, MD: Yeah, there are some interesting studies that reflect on that information. For many of these mutations, it may pretend a risk of developing metastatic disease, it may indicate differences in responsiveness to therapies. But the reality is, we are either stuck with metastatic disease or it hasn’t recurred. There definitely is influence on the treatment response to different drugs, which we’ll come to in a few minutes. But that’s probably the most important part for the mutational analysis.

In addition to some of the risk for developing metastatic disease, which as I mentioned may be lower in PGFR-alpha mutant GIST [gastrointestinal stromal tumor]. It may be higher in SDH-deficient GIST, but those tend to be indolent tumors that they can take many years to develop or progress to clinically meaningful sizes. The mutations have a lot of influence on the biology of the tumors as well as on the responsiveness to therapies.

Shreyaskumar Patel, MD: Absolutely. The 1 example we can highlight is that while KIT exon 11 is the most common mutation we will see, the specific dilution in exons 557, 558, for example, are clearly predisposed to developing later recurrence than usual, right? Those are the kinds of nuances that come from larger experiences over a longer period of time. But that was a very good summary of the mutational analysis in this complex tumor that would appear to be simple on the surface.

Transcript edited for clarity.

Andrew Wagner, MD, reports the following disclosures: Consulting with Deciphera, Daiichi-Sankyo, NanoCarrier. He also reports research funding to his institution with Daiichi-Sankyo, Eli Lilly, Karyopharm, Plexxikon, Aadi Biosciences.