Gastrointestinal Stromal Tumors Treatment Protocols

Updated: Sep 21, 2023
Author: Erin V Newton, MD; Chief Editor: N Joseph Espat, MD, MS, FACS 

Treatment Protocols

Treatment protocols for gastrointestinal stromal tumors (GISTs) are provided below, including those for limited-stage disease and persistent or metastatic disease. For any patient in whom systemic therapy is contemplated, mutational testing is recommended to help guide medication choices.

Limited-stage disease with possible resection

Surgery is the primary treatment for localized or potentially resectable GISTs. Patients with a small GIST (< 2 cm) may be treated with endoscopic surveillance if high-risk features are absent; high-risk endoscopic ultrasound features include the following[1, 2, 3] :

  • An irregular border
  • Cystic space
  • Ulceration
  • Echogenic foci
  • Heterogeneity

Neoadjuvant therapy[4, 5] :

  • Neoadjuvant imatinib therapy is preferred for marginally resectable tumors or patients with comorbidities for surgery. [6]
  • Neoadjuvant therapy is aimed at reducing tumor size, which may facilitate complete surgical resection.
  • Treatment should continue until the time of maximal response, which is typically no more than 10-12 months. [7]
  • The usual dose of imatinib is 400 mg PO daily. In patients with a known exon 9 KIT mutation, a dose of 800 mg PO daily can be considered if tolerated. [8]
  • Neoadjuvant imatinib will be less effective and is therefore not recommended in cases of a platelet-derived growth factor receptor–alpha (PDGFRA) D842V mutation or a succinate dehydrogenase (SDH)–deficient or neurofibromatosis (NF)-related GIST [9, 10, 11]

Adjuvant therapy for high-risk patients[12] :

  • Imatinib is also approved for adjuvant therapy in patients with GISTs
  • Imatinib 400 mg PO daily for 3 years following complete gross resection of CD117-positive GIST has shown an improvement in overall survival and recurrence-free survival compared with a treatment duration of 1 year [13, 14]
  • Extending adjuvant imatinib to 5 years has been shown to continue preventing (or delaying) recurrences, but nearly half of those treated discontinued the imatinib early due to toxicity. [15, 16]
  • Adjuvant imatinib will be less effective and is therefore not recommended in cases of a PDGFRA D842V mutation or an SDH-deficient or NF-related GIST. [9, 10, 11]

Persistent or metastatic disease

The primary treatment for metastatic GISTs is imatinib. Surgery may be indicated in patients who have locally advanced or previously unresectable disease after a positive response to preoperative imatinib, or with limited disease progression on systemic therapy.[1]

Recommended therapy:

  • Imatinib 400 mg PO daily[17, 18, 19, 20] : For patients with a known KIT exon 9 mutation, dose can be escalated to 800 mg (400 mg PO BID)[8]

  • Progression of disease on imatinib 400 mg PO daily: May escalate dose to 800 mg (400 mg PO BID daily) as tolerated

  • In patients with a known PDGFRA D842V mutation conferring imatinib resistance, sunitinib is a reasonable option. Some data indicate that dasatinib may have some activity in this population, as well.[21, 22]

  • In patients with an SDH-deficient or NF-related GIST, imatinib is not recommended because of resistance.[10, 11]  In this situation, sunitinib or regorafenib would be options.[23, 24]

  • Sunitinib 50 mg PO daily for 4 wk, then 2 wk off (4/2 schedule); efficacy and better tolerance have been reported with off-label continuous dosing at 37.5 mg PO daily[25, 26]

  • Regorafenib: 160 mg PO daily for the first 21 days of each 28-day cycle; indicated for locally advanced, unresectable GISTs that no longer respond to imatinib or sunitinib[24]

  • Avapritinib: 300 mg PO daily continued until disease progression or unacceptable toxicity; indicated for unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutations, including PDGFRA D842V mutations[27, 28]

  • Ripretinib: 150 mg PO daily continued until disease progression or unacceptable toxicity; indicated for advanced GISTs for patients previously treated with 3 or more kinase inhibitors [29]

Progressive disease

Options are limited for patients with progressive disease whose GISTs are resistant to both imatinib, sunitinib, and regorafinib. Possible approaches include the following[30]

  • Enrollment in a clinical trial
  • Rechallenging with imatinib and sunitinib if all other options have failed
  • Use of sorafenib, dasatinib, or nilotinib, for patients who do not receive clinical benefits from imatinib and sunitinib