Adjuvant imatinib impacts short-term free from relapse in patients with localized, surgically resected, high/intermediate-risk gastrointestinal stromal tumors (GIST), according to interim results of an intergroup trial. The high-risk subgroup had a nonstatistically significant trend that favored the adjuvant arm regarding imatinib failure-free survival. This trial was presented Monday, June 3, at the 2013 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

This trial used a new end point for the adjuvant setting of survival free from any failure of the first employed tyrosine kinase inhibitor. This end point was designed to incorporate secondary resistance, which is currently the main factor affecting the prognosis of patients with GIST.

Standard treatment for patients with GIST, which are sarcomas of the gastrointestinal wall, is surgery. Neither chemotherapy nor radiation therapy work well for these patients, but trials by the European Organisation (EORTC) for the Research and Treatment of Cancer had shown that a targeted therapy, the tyrosine kinase inhibitor imatinib, is effective in treating patients with advanced GIST. This intergroup randomized controlled phase III trial, known as EORTC 62024, then took the logical next step of determining whether imatinib would also be effective as an adjuvant to surgery in patients with local disease.

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Originally, the primary end point for this trial was overall survival; relapse-free survival, relapse-free interval, and toxicity were secondary end points. In 2009, however, the Independent Data Monitoring Committee, noting the prognostic improvement of patients with advanced GIST, authorized a change in the primary end point to imatinib failure-free survival. Imatinib failure was defined as the time when treatment with a different tyrosine kinase inhibitor began.

Between 2005 and 2008, 908 patients with localized, surgically resected, high/intermediate-risk GIST were randomized to the imatinib (400 mg imatinib daily, 454 patients) or observational (no further therapy after surgery, 454 patients) treatment arms. A total of 835 patients were eligible.

This planned interim analysis was conducted after the occurrence of 115 events according to the imatinib failure-free survival primary end point with a significance level of 1.5%. At a median follow-up of 4.7 years, the 5-year imatinib failure-free survival was 87% in the imatinib arm and 84% in the observational arm (HR=0.80, 98.5% CI [0.51; 1.26], P=0.23).

At three years, relapse-free survival was 84% in the imatinib arm and 66% in the observational arm, while at five years relapse-free survival was 69% in the imatinib arm and 63% in the observational arm (P<0.001). The 5-year overall survival was 100% versus 99%.

The trial included 528 patients with high-risk GIST as determined by local pathology, and for these patients the 5-year imatinib failure-free survival was 79% (imatinib arm) versus 73% (observational arm) (P=0.11). Among 682 patients with centrally reviewed pathology, there were 336 patients with high-risk GIST, and the 5-year imatinib failure-free survival in these patients was 77% (imatinib arm) versus 73% (observational arm) (P=0.44). In the imatinib arm, 17% of the patients stopped early due to toxicity or refusal.