Gastrointestinal Stromal Tumors Treatment Protocols 

Updated: Feb 26, 2018
  • Author: Erin V Newton, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment Protocols

Treatment protocols for gastrointestinal stromal tumors (GISTs) are provided below, including those for limited-stage disease and persistent or metastatic disease.

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 i matinib 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 has also been 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 or olaratumab 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]

Progressive disease

See the list below:

  • Options are limited for patients with progressive disease whose GISTs are resistant to both imatinib, sunitinib, and regorafinib.
  • Other options include the use of sorafenib, dasatinib, or nilotinib for patients who do not receive clinical benefits from imatinib and sunitinib
  • Patients continuing to progress should be recommended to enroll in clinical trials
  • Some studies recommend rechallenging patients with imatinib and sunitinib if all other options have failed