Depuis la découverte de l’efficacité remarquable de l’imatinib dans les tumeurs stromales gastro-intestinales (GIST) avancées à la fin du dernier millénaire, des centaines d’études et de recommandations ont fait avancer nos connaissances sur la prise en charge de cette pathologie. Grâce à cet inhibiteur de tyrosine kinases, des progrès considérables ont été accomplis en une vingtaine d’années, que ce soit dans la définition et la classification de ces tumeurs, dans la compréhension de leurs mécanismes moléculaires et dans la prise en charge thérapeutique des patients atteints de cette néoplasie rare. Le traitement des GIST constitue toujours en 2023 le modèle de thérapie ciblée en oncologie. Plus de 90 % des patients traités par imatinib en situation de rechute bénéficient de cette thérapie ciblée en première ligne de traitement et leur médiane de survie est passée de 18 mois avant 2000 à plus de 75 mois en 2023. Cette révolution thérapeutique qui a transformé le devenir des patients métastatiques a conduit à reconsidérer les attitudes médicales et chirurgicales et la durée de la prise en charge de ces patients. Les avancées successives observées dans les GIST ont ouvert parallèlement des perspectives considérables dans d’autres pathologies tumorales.

Since the discovery of the remarkable efficacy of imatinib in metastatic gastrointestinal stromal tumors (GIST) at the end of the last century, many relevant and critical studies have further advanced the management of this disease. Thanks to this tyrosine kinase inhibitor, considerable progress has been made in twenty years, 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 75 months compared to only 18 months before the imatinib era. This revolution has transformed the outcome 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 at least 3 years after resection of localized GIST reduced the recurrence rate by 70% in patients with a significant high 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. Mutational analysis has a predictive value for sensitivity to imatinib and other molecular-targeted therapies as well as a prognostic relevance. Its inclusion in the diagnostic work-up of all GISTs should be considered standard practice. Successive advances in GIST therapy have created significant opportunities for the treatment of other malignancies.