GIST: Treatment Considerations

Margaret von Mehren, MD: For patients with GIST [gastrointestinal stromal tumor], we think very much, especially in the metastatic disease setting, about using systemic therapy. That is very important. When these agents were first available, we thought less and less about the role of surgery. Before tyrosine kinases were available, surgery was really the only effective option that these patients had. With tyrosine kinase inhibitors being so effective, we sort of forgot about use or how to combine them. Over time, however, we’ve really come to understand a couple of things. We do see patients for whom the disease is controlled, for the most part, but maybe there’s 1 lesion that has started to progress. So do you give up on the agent the patient is on that seems to be controlling most of the disease, or can you consider another form of therapy, such as surgery? I think increasingly, we do that based on the benefit to the patient.

Certainly, with imatinib, it is very straightforward. There are no issues in terms of potentially increased risk of bleeding or wound-healing issues. Patients can take their therapy up to the night before surgery—at least that’s our standard practice where I work—and then resume it as soon as they are able to eat and drink normally and the surgeon is comfortable with them doing so.

It’s a bit more complicated in patients who are on Sutent [sunitinib] and regorafenib, because they do have some VEGF targets. And so, there are potentially some issues with wound healing and/or bleeding. So we’re a bit more conservative with these patients. Typically, within 5 to 7 days before surgery, one would have them hold their therapy. And then, most surgeons want to make sure that patients have good wound healing before they resume therapy.

I think the other thing that we think about are other forms of localized therapy, in particular liver-directed therapy. Our interventional radiologists have techniques for embolization, sometimes radiofrequency ablation, and occasionally there is a role for radiation therapy as well. So working with a multidisciplinary team that is thinking about all of these modalities with you is helpful to make sure that we’re giving the best to our patients.

Certainly, when a patient presents and we’re thinking about what the best therapy is, typically when a patient has metastatic disease we will start with systemic therapy and then do surgery. There are certainly times when surgery needs to be the first thing we do, including if a patient is presenting with obstruction. This is not terribly common with GIST, but there are patients who may present with perforation. Certainly, a perforated tumor can be a medical emergency and should be treated as such, even in the setting of metastatic disease.

Transcript edited for clarity.

Case: A 68-Year-Old Man With Gastrointestinal Stromal Tumor

Initial presentation

• A 68-year-old man complains of a 5-month history early satiety and vague abdominal pain
• PMH: hypertension, medically controlled; colonoscopy at age 55 unremarkable; no family history of cancer
• PE: diffuse abdominal pain on palpation; otherwise unremarkable
  
  

Clinical workup

• Labs: Hb 10.1 g/dL, plt 100 x 109/L; other lab values WNL
• Endoscopy: showeda submucosal ~ 5 cm mass with ulceration
• EUS-FNA biopsy: irregular borders on extraluminal surfaces of the stomach with evidence of heterogeneous echogenicity
• Biopsy showed gastrointestinal tumor with mitotic activity showed >5 mitoses/50 HPFs
• Abdominal/pelvic CT confirmed a 5.4 cm lesion in the body of the stomach
• MRI showed evidence of peritoneal metastases
• IHC and genetic mutational analysis: KIT exon 11 mutation
• ECOG 0
  
  

Treatment

• He was started on imatinib 400 mg PO qDay, continued for 26 months until he complained of increased abdominal pain and decreased appetite
  • ECOG 1; Imatinib was discontinued due to progressive disease
• Treatment with sunitinib 50 mg PO qDay for 4 weeks, with a 2-week drug-free interval was started
  • Treatment was well tolerated for 9 cycles when he developed an altered sense of taste, occasional vomiting and diarrhea; sunitinib was discontinued
• Regorafenib 160 mg (four 40 mg tablets) PO qDay for the first 21 days of each 28-day cycle was started and tolerated except for hand-foot syndrome
  • Regorafenib was discontinued on progression of disease
• The patient was started on ripretinib 150 mg PO qDay