Discontinuation of imatinib therapy puts patients with advanced gastrointestinal stromal tumors (GIST) at high risk for rapid disease progression and is not recommended unless substantial toxicity develops, according to French researchers.
After nearly 3 years of follow up, 2-year progression-free survival was 80% in patients who remained on imatinib but only 16% in those whose treatment was stopped.
In this open-label phase 3 study, 50 patients with advanced GIST who had been free of disease progression during 3 years of treatment with imatinib 400 mg/day were randomly assigned to continue or discontinue therapy. The results of the study by Alex Le Cesne, MD, of Insitut Gustave Roussy, Villejuif, France, are reported in the September 22 online edition of The Lancet Oncology.
Of 25 patients who discontinued therapy, 21 had disease progression after a median 35 months of follow up compared with seven of 25 who remained on treatment. Median time to progression was 9 months after randomization in the discontinuation group but was not reached in the continuous therapy group.
Imatinib was reintroduced in 20 of the 21 patients who relapsed, and after 3 months, all 20 had complete or partial responses or stable disease. Time to secondary resistance was similar in patients who continued and discontinued therapy. This indicates that discontinuation of therapy “neither prevents nor promotes” the development of imatinib resistance, according to the authors.
Because of the high risk of rapid disease progression in patients with advanced GIST when treatment is stopped, they advise that treatment should not be discontinued outside clinical trials unless patients experience significant toxic effects.