Researchers affiliated with the American College of Surgeons Oncology Group (ACOSOG) Intergroup GIST Study Team have reported that adjuvant Gleevec® (imatinib mesylate) improves recurrence-free survival of patients with gastrointestinal stromal tumors (GIST).[1] The details of this study appeared in an early online publication in The Lancet on March 19, 2009.

Gastrointestinal stromal tumors are a unique subset of cancers that arise in the gastrointestinal tract from the cells of Cajal, or the pacemaker cells of the gastrointestinal tissue. Standard treatment for GISTs includes the surgical removal of the cancer, chemotherapy, and/or radiation therapy. However, GISTs tend to be aggressive in nature and resistant to radiation and chemotherapy, with only 4.8% of cases responsive to chemotherapy. Patients with an advanced GIST have an average survival of nine to 20 months following standard treatment.

The majority of GISTs have a mutation within a protein called c-KIT. C-KIT is involved in biological processes that facilitate the growth and multiplication of healthy cells. Normally, this growth process is kept under strict control; however, c-KIT mutations involved with GISTs lead to excessive, uncontrolled multiplication of cancer cells. In 2002, the Federal Drug Administration (FDA) approved Gleevec for the treatment of metastatic and/or inoperable GISTs. Recently, other targeted agents have also been shown the have significant antitumor effects in patients with GIST.

The current study sought to determine the benefit of adjuvant Gleevec in patients with GIST of 3 centimeters or more undergoing definitive surgery. All patients were positive for c-KIT by immunohistochemistry. Three hundred fifty-nine patients were randomly allocated to receive adjuvant Gleevec and 354 to receive placebo for one year after surgical resection. Patients in the placebo arm crossed over and received Gleevec at relapse. The median follow-up of this study was 20 months with a maximum of 56 months. The relapse rate was 8% in the Gleevec group and 20% in the placebo group. Recurrence-free survival was 98% at one year for the Gleevec group and 83% for the placebo group. The most common side effects were dermatitis, abdominal pain, and diarrhea. These authors concluded that “Adjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after resection of primary gastrointestinal stromal tumor.”

Comments: These are potentially very important data for patients with GIST. Further follow-up will be needed to determine if patient survival is also improved by adjuvant treatment versus treatment at the time of relapse.

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