(ChemotherapyAdvisor) – Patients with gastrointestinal stromal tumor (GIST) with a high risk of GIST recurrence who received three years — vs. one year — of treatment with adjuvant imatinib had improved recurrence-free and overall survival, investigators reported in the March 28 issue of JAMA.

Between February 2004 and September 2008, the open-label Phase 3 trial, conduced at 24 hospitals in Finland, Germany, Norway, and Sweden, randomly assigned 400 patients with KIT-positive GIST removed at surgery who were at risk of GIST recurrence to oral imatinib 400mg/day for either 12 months (n=200) or 36 months (n=200). Treatment was initiated within 12 weeks of surgery.

In December 2010, median follow-up was 54 months. A central pathology review confirmed a diagnosis of GIST in 382 of 397 patients (96%) in the intent-to-treat population. Of 366 tumors available for testing, KIT or PDGFRA mutation was detected in 333 (91%).

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Patients in the 36-month group had longer 5-year recurrence-free survival, the primary end point, vs. those assigned to receive imatinib for 12 months, 65.6% vs. 47.9%, respectively (HR=0.46; P<0.001). Fewer patients assigned to 36 months of imatinib administration died during the follow-up vs. those assigned to the 12-month group (12 vs. 25, respectively), and overall survival was longer in the 36-month group (five-year survival, 92.0% vs. 81.7%, respectively; HR, 0.45; P=.02).

In general, imatinib was well tolerated; however, 51 patients (25.8%) assigned to the 36-month group and 25 (12.6%) to the 12-month group discontinued imatinib for a reason other than GIST recurrence that included adverse effects, patient preference, and other or unspecified reason.

The researchers noted that effect on overall survival was based on a relatively small number of deaths, and study patients will continue to be followed to confirm overall survival benefit. “Because GIST recurrence is frequent after discontinuation of adjuvant imatinib, studies that evaluate still longer treatments are warranted, as are studies that address novel agents and their combinations,” they concluded.

An accompanying editorial notes that these trial results have established three years of imatinib 400mg/day as the new standard of care for postoperative treatment of patients with resected high-risk GIST. The U.S. Food and Drug Administration recently approved adjuvant use of imatinib in adults after resection of KIT-positive GIST.


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