What is the treatment for Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

The treatment of gastrointestinal stromal tumors (GIST) typically involves a multidisciplinary approach combining surgery and targeted therapy, with the primary treatment for localized GIST being complete surgical resection and imatinib (Gleevec) as the first-line treatment for metastatic or unresectable GIST, started at 400 mg daily. For localized GIST, complete surgical resection is the primary treatment, aiming to remove the entire tumor with negative margins while preserving organ function when possible, as recommended by the most recent guidelines 1. The decision to use adjuvant imatinib therapy should be based on the risk of relapse, with high-risk patients benefiting from 3 years of adjuvant imatinib therapy 1. Some key points to consider in the treatment of GIST include:

• The importance of mutational analysis in guiding treatment decisions, particularly for patients with KIT exon 9 mutations or PDGFRA D842V mutations 1
• The use of imatinib as the first-line treatment for metastatic or unresectable GIST, with sunitinib and regorafenib as second- and third-line options, respectively 1
• The role of surgery in the treatment of GIST, including the use of laparoscopic excision and the importance of R0 resection 1
• The management of side effects associated with targeted therapies, including fatigue, edema, diarrhea, and skin reactions 1
• The importance of regular follow-up, as GIST can recur even years after initial treatment 1. In terms of specific treatment recommendations, imatinib at 400 mg daily is the standard upfront treatment for locally advanced inoperable and metastatic disease, with the option to increase the dose to 800 mg daily in patients with KIT exon 9 mutations or to switch to sunitinib or regorafenib in patients who progress on imatinib 1. Additionally, regorafenib at 160 mg daily for 3 out of every 4 weeks is the standard third-line therapy for patients progressing on or failing to respond to imatinib and sunitinib 1. Overall, the treatment of GIST requires a multidisciplinary approach, with careful consideration of the patient's individual risk factors and mutation status to guide treatment decisions.

From the FDA Drug Label

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) is regorafenib (STIVARGA), specifically for patients with locally advanced, unresectable, or metastatic GIST who have been previously treated with imatinib mesylate and sunitinib malate 2, 2.

• Key points:
  • Indication: locally advanced, unresectable, or metastatic GIST
  • Previous treatments: imatinib mesylate and sunitinib malate
  • Treatment: regorafenib (STIVARGA)
• Alternative treatment: sunitinib malate capsules are indicated for the treatment of adult patients with GIST after disease progression on or intolerance to imatinib mesylate 3.

From the Research

Treatment Options for Gastrointestinal Stromal Tumor (GIST)

The treatment for GIST depends on the stage and location of the tumor. The main treatment options include:

• Surgical resection: This is the primary treatment for localized primary GISTs 4
• Tyrosine kinase inhibitors (TKIs): These are used to treat unresectable or metastatic GISTs. The standard therapy includes:
  • First-line: imatinib 5, 6, 7, 4
  • Second-line: sunitinib 5, 6, 4
  • Third-line: regorafenib 5
  • Fourth-line: ripretinib (for metastatic GIST) 6
  • Avapritinib (for metastatic GIST with PDGFRA exon 18 mutation) 6
• Other treatment options:
  • Radiotherapy
  • Chemotherapy
  • Hepatic artery embolization
  • Chemoembolization
  • Radiofrequency ablation 8
  • Endoscopic modalities of resection (for small GISTs) 8

Factors Affecting Treatment Outcomes

Several factors can affect the treatment outcomes for GIST, including:

• Tumor size
• Mitotic rate
• Tumor location
• Kinase mutational status
• Occurrence of tumor rupture 7, 4
• Response to TKI therapy
• Completeness of resection
• Surgical complexity 6

Multidisciplinary Approach

A multidisciplinary team approach is essential for the effective treatment of GIST, involving radiologists, medical oncologists, pathologists, and surgeons 6, 4. 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.