Current Treatment Options in the Management of GIST
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Surgery Is Standard of Care for Resectable Primary GIST

Surgery remains the treatment of choice for primary resectable GIST. However, primary GISTs have a high risk of metastatic relapse after initial surgery for localised disease⁶.Surgery for metastatic or recurrent GIST is not curative: as at this stage the cancer has become a systemic disease. More than half of all GIST patients present with advanced GIST. Surgery alone is generally not curative: the 5-year survival rate after complete resection is variable and ranges from 50% to 65% for localised primary GIST and decreases to approximately 35% for advanced GIST³.

Several surgical principles apply to the management of patients with primary GIST. These principles include^3,4:

• Complete gross resection of the tumour and pseudocapsule
• Thorough inspection of the peritoneal surfaces and liver to identify metastasis
• En bloc resection of adjacent tissue should GIST become adherent to nearby structures
• Wide margins are not necessary for disease clearance, but achievement of clear margins may require consideration of complete or partial organ sacrifice^3,4
• Lymphadenectomy is generally not necessary because regional lymph node involvement is rare⁶

Surgery continues to be the therapy of choice in patients with resectable GIST. However, the curative potential of surgery is seldom realised due to a high rate of recurrence and a 5-year survival rate of approximately 54%⁵.

Glivec: Effective Systemic Therapy Becomes the Standard of Care for Advanced GIST

The management of patients with GIST has evolved dramatically since the introduction of Glivec^® (imatinib) in 2002. Before this, nonspecific chemotherapy, surgery, and radiation therapy were the only modalities available. While surgery remains the therapy of choice in resectable tumours, the role of chemotherapy and radiation therapy has been limited by a lack of efficacy and intolerable toxicity.

Glivec is a potent inhibitor of several tyrosine kinases that are commonly associated with GIST, such as KIT and PDGFR. Clinical trial results have shown Glivec to be effective and safe in the management of unresectable and/or malignant metastatic GIST. At 52-month follow-up of the pivotal phase 2 B2222 trial, 84% of patients had a best response of stable disease or better: 2 patients (1%) achieved complete response, 98 patients (67%) achieved partial response, and 23 patients (16%) achieved stable disease^31,32. Current guidelines recommend continued use of Glivec until progression, intolerance, or patient refusal⁶. A treatment algorithm for patients diagnosed with GIST delineates optimal management of patients with GIST and Glivec²⁹, including:

• Initial treatment of metastatic or inoperable GIST with 400 mg or 600 mg Glivec
• Potential dose escalation of Glivec to 800 mg upon disease progression
• Clinical trials of Glivec as adjuvant or neoadjuvant treatment for GIST
• Clinical trials of Glivec therapy as part of a combination regimen or newer targeted agents upon disease progression at 800 mg dose of Glivec

Figure 1. Treatment Algorithm for Patients Diagnosed With Confirmed GIST²⁹

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Several other approaches to the treatment of GIST, especially for the small number of patients who fail to respond or who progress on Glivec, are also under investigation. Many of these are entering clinical trials, and some have shown encouraging activity. These new approaches include:

• Other targeted agents
• Use of Glivec in combination with other therapies

Future management strategies such as adjuvant and neoadjuvant Glivec therapy are aimed at improving outcomes in patients with GIST.

The bleak prognostic picture for patients with malignant GIST has changed with the availability of Glivec, a specific inhibitor of the KIT receptor tyrosine kinase. Glivec is the standard of care for unresectable and/or malignant metastatic GIST.

Read more about Glivec and GIST Treatment.

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