What is a Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

For patients with GIST tumors, the primary treatment approach should involve complete surgical resection for localized tumors, while advanced or metastatic cases should be managed with targeted therapy using tyrosine kinase inhibitors, such as imatinib at 400mg daily, as the standard first-line treatment. This approach is based on the most recent guidelines and evidence, including the study published in 2022 1, which emphasizes the importance of surgical resection and targeted therapy in the management of GISTs.

Key Considerations in GIST Management

• Surgical resection is the primary treatment for localized GISTs, with the goal of achieving a complete resection with minimal functional sequelae.
• For advanced, metastatic, or unresectable GISTs, targeted therapy with tyrosine kinase inhibitors like imatinib is the standard first-line treatment, with a recommended dose of 400mg daily.
• Neoadjuvant imatinib may be considered for locally advanced GISTs to improve the feasibility of surgical resection, with a recommended duration of 6-12 months.
• Adjuvant therapy with imatinib for 3 years may be beneficial for patients with a significant risk of relapse, although the optimal duration and dose require careful consideration based on individual patient factors and mutation status.

Mutation Testing and Treatment Implications

• Mutation testing is crucial in predicting response to treatment, as certain mutations (e.g., KIT exon 9 mutation) may require alternative approaches or dose adjustments.
• Wild-Type GIST, PDGFRA D842V-mutated GIST, succinate dehydrogenase (SDH)-deficient GIST, and Neurofibromatosis (NF-1)-related GIST do not benefit from imatinib treatment, and alternative strategies should be considered.
• The study published in 2016 1 highlights the importance of evidence-based guidelines and expert consensus in the management of GISTs, while the 2022 study 1 provides updated recommendations on the use of targeted therapy and surgical resection.

Monitoring and Follow-Up

• Regular monitoring with CT scans or MRIs every 3-6 months is essential to assess treatment response and detect potential recurrence or progression.
• Close monitoring of the response to neoadjuvant therapy is recommended to avoid delayed local therapy in case of lack of response.

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.

Gist tumor treatment is indicated for patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate, using regorafenib (STIVARGA) 2.

• Key points:
  • Locally advanced, unresectable or metastatic GIST
  • Previously treated with imatinib mesylate and sunitinib malate
  • Treatment with regorafenib (STIVARGA)
• Dosage: The recommended dose is 160 mg STIVARGA (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle 2.

From the Research

Gist Tumor Overview

• Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation 3.
• Most GISTs present asymptomatically and are best identified by computed tomography (CT) scan, with most staining positive for CD117 (C-Kit), CD34, and/or DOG-1 3.

Treatment Options

• Treatment with the tyrosine kinase inhibitor (TKI), imatinib, is the standard first-line treatment for metastatic GISTs 4.
• Sunitinib and regorafenib are multi-kinase inhibitors that can be used as second-line or third-line therapy in imatinib-resistant or -intolerant GISTs, respectively 4.
• Ripretinib (a switch-control tyrosine kinase inhibitor) has recently been approved for fourth-line treatment in metastatic GIST, and the TKI avapritinib has been approved for metastatic GIST harboring the imatinib-resistant PDGFRA exon 18 mutation 4.

Surgical Management

• Macroscopically complete (R0/R1) resection is the standard treatment for localized resectable GIST with adjuvant imatinib therapy recommended for patients with intermediate or high-risk disease 5.
• Cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved 5.
• The role of surgery in metastatic or recurrent disease is more controversial, and case selection is critical, with the potential benefit being difficult to quantify 6.

Post-Surgical Care

• After surgical resection, patients should resume tyrosine kinase inhibitor (TKI) therapy as soon as possible and be monitored for disease progression 4, 5.
• Patients with metastatic GIST should be managed in a multidisciplinary setting, with treatment individualized according to patient age, comorbidities, functional status, symptoms, mutation status, extent of disease, completeness of resection, TKI response, and goals of the patient 4.