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Looking Toward the Future of Advanced GIST Management

Insights From: Brian Van Tine, MD, PhD, Washington University; Jean-Yves Blay, MD, PhD, Centre Leon Berard
Published: Friday, Nov 22, 2019



Transcript: 

Jean-Yves Blay, MD, PhD: What will the next 5 years look like for the treatment of advanced GISTs [gastrointestinal stromal tumors]? That’s an important question because this landscape is completely changing. What are we seeing? We are seeing ripretinib with outstanding results for patients in the fourth line or greater. We can anticipate that probably this treatment and other treatments of this class will be active in earlier phases of the treatment of advanced GIST.

This class of agents will probably become standard in earlier lines. The next question for me is really, what about first-line metastatic phase? And another very important question is going to be, what about adjuvant treatment? And this is a question for the future. I’m not sure it’s going to be for the next 5 years. But that’s going to be something that will be worth exploring, because we know that the reasons are good in the adjuvant setting with imatinib, but still some patients are progressing, and we don’t know at which time it’s best to start the treatment beyond 3 years. We know that 3 years is a standard. Beyond 3 years, as we have randomized trials that are ongoing, so time will tell.

Also, an important aspect is that some GISTs are equipped with mutation outside KIT and PDGF receptor alpha: NF1, BRAF, and TRK. We have treatment for these different forms of GIST, which are going to be adapted to the mutation. Imatinib will not be a 1-size-fits-all treatment for a patient with GIST. This will be probably much more complex in the future.

Brian Van Tine, MD, PhD: I think the next 5 years for the treatment of GIST are going to be very interesting. There’s also the BLU-285 drug that is coming out, avapritinib. I think that we’re going to start actually doing a job of matching the specific point mutations to the right drug. And so as we move forward over the next 5 years, it may turn out that if you have a point mutation at position 7, as opposed to position 11. You may get a different drug in a different order. I think that we’re going to get into this whole new molecular understanding of what patient gets what drug and in what order.

I think this is a field that’s still moving forward very quickly. It’s actually an exciting time to be a gastrointestinal stromal doctor because you actually are beginning to not only drug KIT, but you’re drugging that specific KIT. With the new drugs having new specificities, because they’re really not equal drugs, it’s not just going to be this 1 and then that 1. It’s going to be this patient gets this 1, this 1 patient gets that 1. I really think that we’re going to have a much better understanding and control over how well our patients do, just based on their molecular findings that are at baseline.

Transcript Edited for Clarity  
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Transcript: 

Jean-Yves Blay, MD, PhD: What will the next 5 years look like for the treatment of advanced GISTs [gastrointestinal stromal tumors]? That’s an important question because this landscape is completely changing. What are we seeing? We are seeing ripretinib with outstanding results for patients in the fourth line or greater. We can anticipate that probably this treatment and other treatments of this class will be active in earlier phases of the treatment of advanced GIST.

This class of agents will probably become standard in earlier lines. The next question for me is really, what about first-line metastatic phase? And another very important question is going to be, what about adjuvant treatment? And this is a question for the future. I’m not sure it’s going to be for the next 5 years. But that’s going to be something that will be worth exploring, because we know that the reasons are good in the adjuvant setting with imatinib, but still some patients are progressing, and we don’t know at which time it’s best to start the treatment beyond 3 years. We know that 3 years is a standard. Beyond 3 years, as we have randomized trials that are ongoing, so time will tell.

Also, an important aspect is that some GISTs are equipped with mutation outside KIT and PDGF receptor alpha: NF1, BRAF, and TRK. We have treatment for these different forms of GIST, which are going to be adapted to the mutation. Imatinib will not be a 1-size-fits-all treatment for a patient with GIST. This will be probably much more complex in the future.

Brian Van Tine, MD, PhD: I think the next 5 years for the treatment of GIST are going to be very interesting. There’s also the BLU-285 drug that is coming out, avapritinib. I think that we’re going to start actually doing a job of matching the specific point mutations to the right drug. And so as we move forward over the next 5 years, it may turn out that if you have a point mutation at position 7, as opposed to position 11. You may get a different drug in a different order. I think that we’re going to get into this whole new molecular understanding of what patient gets what drug and in what order.

I think this is a field that’s still moving forward very quickly. It’s actually an exciting time to be a gastrointestinal stromal doctor because you actually are beginning to not only drug KIT, but you’re drugging that specific KIT. With the new drugs having new specificities, because they’re really not equal drugs, it’s not just going to be this 1 and then that 1. It’s going to be this patient gets this 1, this 1 patient gets that 1. I really think that we’re going to have a much better understanding and control over how well our patients do, just based on their molecular findings that are at baseline.

Transcript Edited for Clarity  
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