This evidence-based series was developed by the Sarcoma Disease Site Group (DSG) of Cancer Care Ontario's (CCO's) Program in Evidence-Based Care (PEBC). The series is a convenient and up-to-date source of the best available evidence on imatinib mesylate (Gleevec™) for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours, developed through systematic review, evidence synthesis, and input from practitioners in Ontario.
The Sarcoma DSG focused their discussion on the evidence for imatinib as a treatment for adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST). Three of the trials (two phase III and one phase II) were only available in abstract form. Therefore, full data was not available for all outcomes, thus making pooling of the results inappropriate. The remaining phase II trial was available as a fully published report. The trial received funding from Novartis Oncology. Since those trials constituted the best available evidence for the use of imatinib for gastrointestinal stromal tumours, the Sarcoma DSG agreed that those trials should be included in this practice guideline report.
The Sarcoma DSG also discussed the fact that no trials compared imatinib to no treatment. Therefore, it is not possible to state with absolute statistical certainty that treatment with imatinib confers a definite survival advantage. However, the trials do show response rates ranging from 41% to 58%. If the stable disease rate is added to the response rate, the result is an increase to 73% to 82%. Also, progression-free and overall survival in those trials is markedly higher than in historically untreated patients. Therefore, the Sarcoma DSG agreed that it is reasonable to assume that the observed progression-free and overall survival rates are both relevant and meaningful.
Another point of discussion was the question of dose level. There has been no established benefit for doses higher than 400 mg daily. In addition, the higher toxicity associated with higher doses of imatinib would suggest that there is no clear benefit to starting patients at higher doses. Therefore, the Sarcoma DSG recommends that patients should start on a dose of 400 mg daily.
Finally, in terms of treatment duration, there are limited data to form definitive recommendations for situations such as stable disease, disease that is rendered resectable, or complete remission of disease. However, given the data that are available in the trials conducted to date, as well as the potential toxicity and the difficulty in discerning complete remission with reasonable certainty, the Sarcoma DSG agreed on the following:
- For stable disease, treatment should be discontinued if the disease progresses or toxicity develops.
- For disease that is rendered resectable, surgery should be considered.
- For complete clinical response (CR) and radiologic remission, the discontinuation of therapy two months after CR has been observed would be reasonable.