Prolonged Treatment with Imatinib for High-Risk GIST Increases Survival, Reduces Recurrence
Chicago, IL—Results from a phase 3 clinical trial presented at a plenary session at ASCO 2011 could lead to prolonged treatment with adjuvant imatinib for gastrointestinal stromal tumors (GIST).
The extension of imatinib (Gleevec) treatment to 3 years, compared with the usual 1 year, resulted in a 54% reduced risk of recurrence and 55% reduced risk of death within 5 years for patients with high-risk disease, reported Heikki Joensuu, MD, Helsinki University Central Hospital, Finland.
“These data are pretty compelling,” Dr Joensuu said. “I would not be surprised if the standard will be 3 years of adjuvant imatinib in the near future.”
Mark G. Kris, MD, who moderated a press briefing and is Chair of the ASCO Cancer Communications Committee, agreed. “The entire oncology community was extremely excited when we saw the survival curve and those numbers at 5 years. It’s one of the amazing stories in oncology, and it is the kind of data that change guidelines,” he said.
The Scandinavian Sarcoma Group and Sarcoma Group of the AIO, Germany, conducted the SSGXVIII/ AIO study, a phase 3 open-label clinical trial that evaluated 36 months versus 12 months of adjuvant imatinib administered after surgical resection to 400 patients with GIST at high risk of recurrence.
At a median follow-up of 54 months, recurrences or death occurred in 50 of 198 (25%) patients receiving 36 months of imatinib compared with 84 of 199 (42%) patients receiving only 12 months of treatment.
The recurrence-free survival rate was 86.6% at 3 years and 65.6% at 5 years with 36 months of treatment compared with 60.1% and 47.9%, respectively, with 12 months of treatment, representing a significant 54% reduction in risk of recurrence (P <.001).
Overall survival was 96.3% at 3 years and 92.0% at 5 years with 36 months of treatment compared with 94.0% and 81.7%, respectively, with 12 months of imatinib, representing a 55% mortality risk reduction (P = .019). However, grade 3 or 4 adverse events were more common with longer treatment, and more patients discontinued GIST in the 36-month arm.
More May Be Better, Experts
Agreed Charles D. Blanke, MD, Chief of Medical Oncology, University of British Columbia, Vancouver, commented on the study, noting that its conclusions were “valid.” He suggested that oncologists who typically initiate imatinib on relapse might want to rethink this strategy.
“If you have a patient who has high-risk GIST, at least as defined by the study, giving him or her 3 years of imatinib represents the new gold standard,” he maintained. “The overall survival benefit demonstrated with immediate postoperative imatinib means it is no longer acceptable to withhold treatment in the adjuvant setting, hoping to ‘catch up’ when a patient has recurrent metastatic disease.”
He acknowledged, however, continuing treatment for 3 years could be problematic for many patients, as suggested by a higher rate of side effects and more than a doubling in the dropout rate among patients who received imatinib for that long. Although it is possible that treatment even beyond 3 years could be even more beneficial, he noted, “Difficulties on the 3-year arm of SSGXVIII/AIO may bode poorly for therapy lasting even longer.”
“For now, if I were a patient with a resected GIST and I had a compliant oncologist, I would request more,” he said. “As a compliant oncologist, I personally will offer patients treatment… indefinitely.”