[Medical therapy of GIST; from palliative to curative treatment]

Since the discovery of the remarkable efficacy of Imatinib in metastatic GIST at the end of the last century, dozens of studies have further advanced the management of this disease. Considerable progress has been made in the last dozen years thanks to this tyrosine kinase inhibitor, not only in terms of the definition and classification of these tumors, but also in our knowledge of their molecular mechanisms and in the therapeutic management of patients with this rare disease. Treatment of GIST now serves as a model--or even the model--for targeted therapy in oncology. Over 90% of relapsing patients benefit from first-line Imatinib therapy, with a median survival time of 60 months compared to only 18 months before the Imatinib era. This revolution has transformed the outlook of patients with metastatic disease. It has also led to a review of medical and surgical attitudes and prolonged the management of these patients, most of whom will live normally with dormant residual disease. Imatinib should not be interrupted but continued until the tumor progresses or intolerable adverse effects occur. Early studies showed that adjuvant Imatinib therapy given for one year after resection of localized GIST reduced the recurrence rate by 70% in patients with a significant risk of relapse. Administered for three consecutive years, Imatinib even had a significant impact on survival. Despite these results, the optimal duration of Imatinib therapy in the adjuvant setting remains to be defined, as patients who relapse after Imatinib discontinuation remain remarkably sensitive to the same drug In addition to Imatinib (and sunitinib, that has also proven effective in metastatic disease), several other tyrosine kinase inhibitors are in the pipeline. Coupling of these drugs with the GIST molecular profile opens up promising perspectives for the future. Successive advances in GIST therapy have created significant opportunities for the treatment of other tumors.