What is the treatment for gastrointestinal stromal tumor (GIST) of the intestine?

From the Guidelines

The primary treatment for intestinal gastrointestinal stromal tumors (GISTs) is surgical resection with the goal of complete removal with negative margins, and adjuvant therapy with imatinib 400 mg/day for 3 years is recommended for patients with a significant risk of relapse. For localized disease, surgery alone may be curative. The standard treatment of localized GISTs is complete surgical excision of the lesion, with no dissection of clinically negative lymph nodes 1. If laparoscopic excision is planned, the technique needs to follow the principles of oncological surgery 1.

Key Considerations

• R0 excision is the goal, with margins clear of tumor cells at least at the site of origin in the GI tract 1.
• In low-risk GISTs located in unfavorable locations, the decision can be made with the patient to accept possibly R1 (microscopically positive) margins 1.
• Adjuvant therapy with imatinib for 3 years is the standard treatment for patients with a significant risk of relapse, with an ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1 score of A 1.
• The benefit associated with adjuvant imatinib may vary according to the type of KIT/PDGFRA mutation, being greater in patients with KIT exon 11 deletion mutations 1.
• PDGFRA D842V-mutated GISTs should not be treated with adjuvant therapy, given the lack of sensitivity to imatinib of this genotype both in vitro and in vivo 1.

Treatment Approach

• For larger tumors (>3 cm) or those with high-risk features, adjuvant therapy with imatinib (Gleevec) at 400 mg daily for 3 years is recommended to reduce recurrence risk.
• For unresectable or metastatic GISTs, imatinib is the first-line treatment, typically starting at 400 mg daily, which can be increased to 800 mg daily if needed, particularly in the case of a KIT exon 9 mutation 1.
• Treatment response should be monitored with regular CT or MRI scans every 3-6 months.
• Multidisciplinary care involving surgical oncology, medical oncology, and gastroenterology is essential for optimal outcomes, as treatment plans must be individualized based on tumor size, location, mutation status, and patient factors.

From the FDA Drug Label

1.1 Gastrointestinal Stromal Tumor Sunitinib malate capsules are indicated for the treatment of adult patients with gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate.

1.2 Gastrointestinal Stromal Tumors STIVARGA is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

The treatment for gastrointestinal stromal tumor (GIST) of the intestine is:

• Sunitinib for adult patients with GIST after disease progression on or intolerance to imatinib mesylate 2 2.
• Regorafenib for patients with locally advanced, unresectable or metastatic GIST who have been previously treated with imatinib mesylate and sunitinib malate 3. Key points:
• The treatment options are for adult patients.
• Sunitinib and regorafenib are used for GIST after failure of other treatments.

From the Research

Treatment Options for Gastrointestinal Stromal Tumor (GIST) of the Intestine

• The standard treatment for localized resectable GIST is macroscopically complete (R0/R1) resection, with adjuvant imatinib therapy recommended for patients with intermediate or high-risk disease 4.
• For patients with advanced unresectable or metastatic GIST, imatinib has significantly improved outcomes, with approximately half of patients achieving partial response (PR) or stable disease (SD) on imatinib 4, 5.
• Cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved 4, 6.
• The benefit of surgery in patients with focal tumor progression on imatinib is unclear, but may be considered, while patients with multifocal progression undergoing surgery generally have poor outcomes 4.
• Neoadjuvant therapy with imatinib is also being investigated for its effect on surgical outcomes, with first trial results reported 7.
• Complete surgical resection is the treatment of choice for primary GIST, even with current advances in molecular targeting therapy with imatinib and sunitinib 8.
• A multidisciplinary treatment, including surgical resection, is necessary even for the treatment of advanced or metastatic/recurrent GISTs in which the treatment of choice is imatinib therapy 8.
• Surgical treatment is expected to be effective for resectable liver metastases, secondary resistance to imatinib, or residual tumors responding to imatinib 8.

Surgical Management

• Surgical resection as a multidisciplinary treatment is considered to have gained recognition as an important option for metastatic GIST 8, 6.
• The decision to pursue metastasectomy for GIST should be made in a multidisciplinary setting and be individualized according to patient age, comorbidities, functional status, symptoms, mutation status, extent of disease, completeness of resection, TKI response, and goals of the patient 6.
• After surgical resection, patients should resume tyrosine kinase inhibitor (TKI) therapy as soon as possible and be monitored for disease progression 6.
• Debulking/palliative surgery may be necessary for patients with complications of hemorrhage, pain, or intestinal obstruction, but there is no known survival benefit from debulking operations or R2 resections 6.