Progression of Metastatic GIST

Jonathan Strosberg, MD:The patient had stable disease on imatinib for roughly 2 years, but in 2016, she had progressive abdominal pain. CT scan showed growth in the primary tumor as well as a new liver metastasis. Imatinib was stopped and she was started on sunitinib 37.5 mg daily.

So, sunitinib targets the KIT receptor, among other receptors, and it was shown to substantially improve progression-free survival in the placebo-controlled study in patients who either progressed or were intolerant to first-line imatinib. Progression in GISTs can sometimes be a little misleading. We know that there are rare cases where patients initiate first-line therapy and their tumors, particularly liver metastases, can sometimes enlarge but also become more cystic. And in these cases, it’s important not to be misled. The increase in size does not necessarily imply disease progression, and the clue to that is more necrotic appearance to the tumor. Eventually, those tumors often start shrinking subsequently. But after 2 years of treatment, that’s when progression is almost expected in a high-grade GIST. And if the tumors are enlarging without this decrease in tumor enhancement, it probably represents a real progression.

Sometimes, we see specific sites of progression. For example, within a tumor that has become cystic, sometimes you’ll see growth of an enhancing tumor within the cystic tumor, and this really represents a site of resistance that implies localized progression. This patient probably has developed secondary resistance to imatinib. The patient was initially sensitive, and we know that further mutations in the KIT receptor lead to resistance to imatinib.

In the metastatic setting, generally we obtain either CT scans or MRIs of the abdomen and pelvis. In patients with high-grade tumors, we tend to do these scans fairly frequently. In patients with pretty stable—especially lower-grade—tumors, probably every 6 months would be appropriate. In the surveillance setting after curative resection, we tend to adjust our scan frequency to the risk and grade of the tumor. After the first couple of years, patients with relatively low-risk tumors can often be monitored annually and sometimes even less frequently.

Transcript edited for clarity.

August 2014

• A 59—year-old Caucasian female presented with acute onset abdominal pain
• Past medical history was remarkable for hyperlipidemia
  • Her performance status was ECOG 1
• Abdominal CT findings showed an 11-cm mass in the jejunum and a 3-cm lesion in the liver
  • Biopsy confirmed primary gastrointestinal stromal tumor (GIST) in the jejunum
  • The tumor was determined to be unresectable at the time because of its size and location
• IHC was positive for CD117 (c-KIT); molecular analysis demonstrated an exon 11 mutation
• Mitotic activity was high with >5 mitoses/50 high-power fields
• Treatment was initiated with imatinib 400 mg once daily
• No further disease progression was noted

​October 2016

• During routine follow-up, the patient complained of recurring abdominal pain
• Abdominal CT scan showed a slight increase in the primary tumor size and a new small metastatic tumor in the liver
  • Her ECOG performance status was 1
• The patient was switched to sunitinib 37.5 mg and showed stable disease on follow-up imaging at 3 months

March 2017

• At her 6-month follow-up, abdominal CT scan revealed additional metastases in the liver
• ECOG performance status had changed to 2
• The patient was subsequently referred to an academic center for treatment and was switched to regorafenib 160 mg on days 1-21 of every 28-day cycle
• Three weeks after initiating treatment with regorafenib, she complained of increased fatigue
• She presented with hand-foot skin reaction, which presented as tingling, burning sensations on her palms and a decreased tolerance for touching hot objects