Management of a Patient With GIST and KIT Mutations

Anne Mailhot, PA-C, University of Colorado Cancer Center, Aurora, Colorado, presents the case of a patient with gastrointestinal stromal tumor (GIST) with mutations of the KIT gene. PA Mailhot highlights the importance of personalized care and multiple molecular screenings when managing these patients.

Transcript:

My name is Anne Mailhot. I am a physician assistant. I work at the University of Colorado Cancer Center.

This case is regarding a 42-year-old male who presented with 2 months of abdominal pain. Upon CT [scan of the] abdomen/pelvis, this demonstrated a large mass and a biopsy was completed that showed GIST, or gastrointestinal stromal tumor, in the biopsy. This showed an exon 11 mutation [in the KIT gene], which warranted treatment with imatinib since this medication is effective against exon 11-mutant GIST. He remained on this for 3 years.

After 3 years, he was disease free, so the decision was made to stop treatment. Within a year of stopping the medication, he developed a small right lower abdominal mass, which showed to be GIST-positive after a biopsy, and had positive margins. He resumed imatinib at that time and remained on this for another 2 years. He lost access to the medication due to insurance gaps and was intermittently taking the imatinib, just to make it last, until about 6 months later when he experienced progression of disease.

Despite increasing imatinib to appropriate dosing, imaging 2 months later demonstrated continued progression. Therefore, a new biopsy was obtained, which showed a new exon 17 mutation [in the KIT gene]. After a lot of discussion and attempts to proceed with whichever treatment was felt to be right for that point in his course, he started regorafenib. There was a 2-month delay in getting the medication, due to difficulties obtaining the medication, and then 6 months later he had confirmed progression of disease on the regorafenib. So, a very short time-period on this treatment.

At that juncture, he underwent resection and then started on ripretinib in September of 2021. About two years later, an episode of acute abdominal pain prompted imaging, which demonstrated recurrent GIST leading to yet another resection. Testing on this tumor showed a new exon 13 mutation plus a different exon 17 mutation [in the KIT gene]. He was reinitiated on ripretinib, but at a higher dose.

During the course of his treatment with ripretinib, he again experienced difficulty obtaining and affording the medication. And about 6 months later, and at this point we're at about late 2024, he again experienced progression of disease, we're thinking possibly related to the inconsistent dosing that happened over several months when he wasn't able to access the medication. At this point in late 2024, we enrolled him on the clinical trial with sunitinib —reason being, that sunitinib is favorable with certain exon 17 mutations— plus an investigational agent bezuclastinib, and he remains on this treatment now.

Why is personalized care particularly important for patients with GIST?

It's really important to pay attention to mutations when it comes to GIST. Mutations versus wild-types, or non-mutant GIST. Exon 11-mutated GIST has been the most straightforward type of GIST to treat. We have the most and most effective treatments for this type of mutation, but more research has been necessary to target different exon mutations and wild-type GIST especially, which is one of the hardest types to target.

Can you explain how the evolving molecular landscape in GIST affects treatment for these patients?

Why the molecular portion of diagnostics is important for GIST is because it does change the way that you treat a patient. But also, to recognize that the mutations and the molecular makeup of these tumors can change as time goes and as you move forward through different treatments. Re-biopsying or sending new resections to pathology and further molecular testing to see if this tumor is evolving over time, and if it then makes them eligible for different kinds of treatment.

What are some considerations for APPs when managing patients with GIST?

Specific to APPs that are managing patients that have GIST would be toxicity monitoring on certain treatments. Toxicity monitoring should be pretty frequent upon initiating treatment, to ensure that the patient is being compliant. As we know, toxicity can often deter patients from taking medication. It can also cause safety issues and so frequent monitoring in the beginning, and then as tolerance is established, the patient can be given more space from the medical setting, but with continued close monitoring — with scans every 3 to 6 months, depending on where they are in their treatment and their diagnostic course.

Is there anything else you would like to add about this case?

I think this particular case shows the landscape of GIST: that it can very much change over time. Something that works today may not work tomorrow. And while imatinib is great for our exon 11 mutation GIST, that can change with time. The importance of just remaining vigilant in terms of re-biopsying and retesting for molecular mutations. And also just how the landscape for GIST is changing with time, which is a good thing because we have our difficult mutant GIST that we're still learning about, but also our wild-type GIST, which are really, really difficult to treat still.