Use of Targeted Therapy in GIST Mutations

Transcript:Jonathan Trent, MD, PhD: While we’re talking about molecular drivers of sarcomas like epithelioid sarcoma, let’s talk a little more about GIST [gastrointestinal stromal tumor]. There’s recent attention being given to PDGFR [platelet-derived growth factor receptor] D842V mutated GIST with the FDA approval of avapritinib, which is an inhibitor and it seems to be very effective against PDGFR D842V. I wonder what your thoughts are about the agent. I know you participated in the clinical trials like I did.

Neeta Somaiah, MD: Yes.

Jonathan Trent, MD, PhD: What’s been your experience with it?

Neeta Somaiah, MD: As soon as we started treating the patients with the PDGFR D842V mutation with this drug, it was very evident that unlike, not having any standard of care for these patients, we used to treat them with the available TKIs [tyrosine kinase inhibitors] with no great response. Maybe some patients had stable disease for a while, and we had nothing. And then with this drug we actually see responses, significant responses, even CRs [complete responses]. There are around 5% to 8% of all GISTs that do have this PDGFR exon 18 mutation, and the majority are D842V. This drug did get approval for all patients with PDGFR exon 18 mutations because the response rate with avapritinib was close to 90% with D842V, and around 84% for all PDGFR exon 18 mutations.

Jonathan Trent, MD, PhD: Wow, that’s amazing.

Neeta Somaiah, MD: That is now my first choice of therapy for all patients who have been diagnosed with PDGFR D842V, or just exon 18 mutations, which is why it becomes very important that all GIST patients, even if it’s a small percentage, you do not want to miss. And there are some cues. If you have a gastric GIST, if there’s some lymph node involvement, things that cue you in that this patient could likely have a PDGFR mutation. So we do need to check for mutations up front, and now we have a drug that we can treat them with.

Jonathan Trent, MD, PhD: It’s so exciting. How often are you part of the study team that introduces a new drug to the market that has an almost 90% response rate? So rewarding.

Neeta Somaiah, MD: It is. It is extremely rewarding, and it’s extremely rewarding to now follow these patients, some of my patients who had gone through 6 prior TKIs with no response. We were just treating them with whatever we could find, and thankfully they made it to this drug.

Jonathan Trent, MD, PhD: Yes. Avapritinib is unique compared to imatinib, for instance, even sunitinib, because of its ability to really bind to that region of exon 18 and PDGFR, and really bind the kinase, block the ATP [adenosine triphosphate]-binding site, and really shut down the enzyme. It shuts down the PDGFR kinase very efficiently. I think that’s why we’re seeing such great response rates.

Neeta Somaiah, MD: And it was designed as an inhibitor of the PDGFR, and also has very good activity probably against the exon 17 D816 mutation that is resistant to most of the other TKIs. So that’s why we see such good responses.

Transcript Edited for Clarity