Gastrointestinal Stromal Tumors Treatment Protocols
Updated: Nov 10, 2021
Author: Erin V Newton, MD; Chief Editor: N Joseph Espat, MD, MS, FACS
Treatment protocols for gastrointestinal stromal tumors (GISTs) are provided below, including those for limited-stage disease and persistent or metastatic disease.
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] :
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]
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]
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.[22, 23]
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[24, 25]
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[23]
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[26, 27]
Options are limited for patients with progressive disease whose GISTs are resistant to both imatinib, sunitinib, and regorafinib. Possible approaches include the following[29]