Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), Spanish Group for Research on Sarcomas (GEIS)
Mené dans 12 pays sur 908 patients atteints d'une tumeur stromale gastro-intestinale de stade localisé, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans échec de l'imatinib, et la toxicité de l'imatinib en traitement adjuvant (durée médiane de suivi : 9,1 ans)
Résumé en anglais
Background : In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk GIST patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study.
Methods : This was a randomized, open label, multicenter phase III trial performed at 112 hospitals in 12 countries. Patients were randomized to 2 years (yrs) of imatinib, 400 mg daily, or no further therapy after surgery. The primary end-point was imatinib failure-free survival (IFFS), while relapse-free survival (RFS), relapse-free interval (RFI), overall survival (OS) and toxicity were secondary end-points. Adjusting for the interim analyses, results on IFFS were assessed on a 4.3% significance levels; for the other endpoints, 5% was used.
Results : 908 patients were randomized between January 2005 and October 2008, 454 to imatinib and 454 to observation. 835 patients were eligible. With a median follow-up of 9.1 years, 5 (10)-year IFFS was 87% (75%) in the imatinib arm versus 83% (74%) in the control arm (HR=0.87, 95.7% CI [0.65; 1.15], p=0.31); RFS was 70% versus 63% at 5 years and 63% vs 61% at 10 years, (HR=0.71, 95% CI [0.57; 0.89], p=0.002); OS was 93% versus 92% at 5 years and 80% versus 78% at 10 years (HR=0.88, 95% CI [0.65; 1.21], p=0.43). Among 526 patients with high-risk GIST by local pathology, 10-year IFFS and RFS were 69% versus 61%, and 48% versus 43%, respectively.
Conclusions : With 9.1 years of follow-up, a trend toward better long-term IFFS in imatinib-treated patients was observed in the high-risk subgroup. Although the difference was not statistically significant and the surrogacy value of such an end-point is not validated, this may be seen as supporting the results reported by the Scandinavian/German trial, showing a sustained small but significant long-term OS benefit in high risk GIST patients treated with 3 years of adjuvant imatinib.
