Imatinib Therapy for Resectable GIST

Jonathan Trent, MD, PhD: The use of neoadjuvant or preoperative imatinib in patients with gastrointestinal stromal tumor is presented by a number of studies—McCullough et al—that support the use of neoadjuvant, as well as adjuvant therapy in patients with gastrointestinal stromal tumor. In my practice, we use preoperative imatinib therapy fairly frequently, and the duration is not written in stone. We typically will treat the patient to maximum tumor shrinkage, which ends up being 6 to 9 months. About 5 months in this case might be a little early, but the patient clearly had substantial tumor regression. At that point in time, proceeding to surgery is very reasonable.

Adjuvant therapy with a primary tumor is supported by the SSG study that found both a recurrence-free survival benefit, and overall survival benefit for patients treated for 3 years versus 1 year. In this specific situation, the patient has a solitary liver metastasis—this would require longer duration therapy, perhaps a lifetime.

For patients in the metastatic setting, there seems to be little benefit in treatment at higher doses than 400 mg per day, if the patient has anexon 11mutation. So, if this patient, in this case, indeed had anexon 11mutation, I would have initiated therapy with a 400 mg per day dose of imatinib and continued that postoperatively.

In August 2016, after 2 years, this patient was found to have multiple peritoneal implants and a new solitary liver lesion by CT scan of the abdomen and pelvis. This patient still had a reasonable quality of life, was able to perform his activities of daily living, and was only limited really in strenuous activity. The patient was initiated on therapy with sunitinib 37.5 mg continuous daily dosing.

Transcript edited for clarity.

September 2014

• A 64-year old Caucasian male presented with abdominal pain and 3-month history of fatigue
  • PMH was remarkable for hypertension well-controlled with a beta-blocker
  • No family history of cancer
  • He could perform all activities independently
• Abdominal CT findings:
  • 12-cm mass arising from the stomach and involving the cardia, fundus, and body of the stomach
  • 7-cm solitary mass in the left lobe of the liver
• Biopsy results:
  • Gastric GIST with liver metastases
  • IHC positive for CD117 (c-KIT), molecular analysis showed exon 9 deletion
  • Mitotic activity, high with >5 mitoses/50 HPFs
• Treatment was initiated with neoadjuvant imatinib 600 mg daily for 5 months
  • The primary tumor was stable during this time, the liver mass size decreased from 7 cm to 4 cm
• The patient was referred to a surgeon and underwent hepatectomy for the liver metastasis
  • Following surgery, R0 resection with clear margins
• Treatment was initiated with imatinib 800 mg daily

August 2016

• Abdominal CT imaging findings:
  • Multiple peritoneal implants
  • A new small nodule (<1 cm) in the liver
• The patient could perform all activities independently with small occasional breaks, but could not perform physically strenuous activities
• He was switched to sunitinib 37.5 mg daily

February 2017

• At his 6-month follow-up, the patient was still able to perform most non-strenuous activities independently; however, the frequency of being able to do so had declined significantly
• Abdominal CT scan showed progression in multiple peritoneal implants; the liver nodule increased in size to 2 cm
• He was referred to an academic center
  • His treatment was switched to regorafenib 160 mg, 3 weeks on, 1 week off
• The patient appeared to tolerate therapy well, after initial dose modification due to diarrhea experienced during the second week of therapy
• At the 6-month follow-up:
  • Abdominal CT scan showed slight reduction in the peritoneal implants
  • The liver nodule was no longer visible