The Future of Treatment for Soft Tissue Diseases


Neeta Somaiah, MD: While we’re on the topic of PDGFR [platelet-derived growth factor receptor]-mutated GIST [gastrointestinal stromal tumor], what other exciting developments are there for KIT-mutated GIST as well that are on the horizon? What are your thoughts about the INVICTUS data that have been presented with the drug ripretinib?

Jonathan Trent, MD, PhD: That’s a very good point for us to discuss because as of today we have imatinib, sunitinib, regorafenib, and that’s all that patients with GIST have when they’re advanced or inoperable. Unless they have a PDGFR D842V mutation, those 3 don’t work, but they do have avapritinib.

But there’s another agent that’s on the horizon, ripretinib. And ripretinib is being studied in 2 different clinical scenarios. One is fourth line versus placebo, the INVICTUS study. And those data have been presented at a couple of meetings and have shown clear activity compared to placebo in terms of response rates, in terms of progression-free survival, in terms of overall survival.

We don’t know what’s going to happen at FDA review, but I think there’s a pretty good chance that it will be approved. And then we’ll have a fourth-line agent for patients with metastatic inoperable GIST.

Neeta Somaiah, MD: Fourth line and beyond has a 9% response, which even though it seems low, I think it is quite encouraging because we didn’t have anything in that space before. And the progression-free survival is over 6 months. It was sad to see patients on placebo fall off so fast, but that just tells us that these patients with KIT-mutated GIST do need a TKI [tyrosine kinase inhibitor] and shouldn’t be taken off their TKI because they’ll progress quite fast.

Jonathan Trent, MD, PhD: And a 6-month progression-free survival in fourth line, remember sunitinib in second line was a 6-month progression-free survival. I think it’s pretty clear that this agent has some activity and has a place, at least in fourth line.

Neeta Somaiah, MD: Right, yes.

Jonathan Trent, MD, PhD: Now the question is, it’s also being studied in INTRIGUE, which is a second-line study of ripretinib versus sunitinib in patients with imatinib-resistant GIST. We’ll have to see whether this new exciting agent that has a different mechanism of action, it binds to the switch pocket, not to the ATP [adenosine triphosphate]-binding pocket….

Neeta Somaiah, MD: Right, it’s blocking both, so dual action there.

Jonathan Trent, MD, PhD: Yes, whether it’s more active than sunitinib. We’ll just have to wait and see about that one.

Neeta Somaiah, MD: And the rationale to bring it into second line was also because of a favorable adverse effect profile. Ripretinib appears to have much lower hand-foot syndrome, and might have a little hypertension, but is otherwise really well tolerated.

Jonathan Trent, MD, PhD: Yes.

Neeta Somaiah, MD: There was a 50% or higher alopecia rate, which is unusual for our patients, but that’s something interesting. But so far most patients have tolerated it well, and haven’t minded losing their hair. So we’ll see how it does against sunitinib.

Jonathan Trent, MD, PhD: Yes, I’m very excited for those results. Now also we’ve talked about avapritinib already in the setting of PDGFR D842V-mutated GIST.

But it’s also being studied in third line, inoperable metastatic GIST, against regorafenib. Again, in the phase III, VOYAGER, randomized, controlled trial. That’s ongoing, it’s accrued a lot of patients very quickly.

Neeta Somaiah, MD: It’s actually completed accrual now. So we’re going to get the data sometime this year, I’m hoping.

Jonathan Trent, MD, PhD: Maybe at ASCO [the American Society of Clinical Oncology annual meeting].

Neeta Somaiah, MD: Maybe.

Jonathan Trent, MD, PhD: Maybe not.

Neeta Somaiah, MD: Maybe at ASCO later this year, yes.

Jonathan Trent, MD, PhD: It’ll be exciting to see if we have another new agent in third line.

Neeta Somaiah, MD: Right, because they did report, in the phase I/II study with avapritinib, the response rate for second- and third-line patients was actually quite high, even patients with KIT mutation were within the 20% range. So it will be good to see. It seems more than what we’ve seen with regorafenib in the past, so I’m waiting to see these results to see if what we saw with the phase I study actually pans out in their phase III study.

Jonathan Trent, MD, PhD: Yes.

Neeta Somaiah, MD: Then in the future they also have plans to test avapritinib in the second-line setting against sunitinib. That’s a study that is on hold for now, but we’ll see what that data show in the future once it starts accruing.

Jonathan Trent, MD, PhD: Yes, it’s great to see so many new therapeutic opportunities for our patients with GIST.

Neeta Somaiah, MD: Yes.

Jonathan Trent, MD, PhD: And I know that there are other studies that are non-TKI [tyrosine kinase inhibitor] in the pipeline. There are some studies looking at dual checkpoint inhibitors. There are studies looking at other immunotherapy approaches. There are even CAR [chimeric antigen receptor] T-cell studies that people are developing in the laboratory. Now those are certainly not ready for prime time yet, but it’s really good to see those in the future, even past TKI therapy.

Neeta Somaiah, MD: Correct, yes. It’s an exciting field with newer agents, and I think our challenge is going to be how to select the correct treatment for patients up front to delay development of resistance as much as we can. And then choose the second-line therapy according to their mutation status.

Jonathan Trent, MD, PhD: True, another role potentially for liquid biopsy.

Neeta Somaiah, MD: Perhaps, yes.

Jonathan Trent, MD, PhD: Perhaps. Well, this has been an excellent discussion. We hope that you found the information presented in this webinar to be valuable to your clinical practice. Thank you for watching this OncLive® NewsNetwork program.

Transcript Edited for Clarity

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