Imatinib Mesylate or Observation Only in Treating Patients Who Have Undergone Surgery for Localized Gastrointestinal Stromal Tumor
Phase 3N = 908NCT00103168
- Population
- Patients with localized, intermediate- or high-risk GIST after R0-R1 surgery (835 of 908 randomised patients were eligible)
- Design
- Randomised, open-label, multicentre phase III trial at 112 hospitals in 12 countries: 2 years of imatinib 400 mg daily or no further therapy after R0-R1 surgery. The primary endpoint was overall survival at the start and was changed in 2009 to imatinib failure-free survival, with agreement of the independent data monitoring committee.
- Primary endpoint
- IFFS
- Arms
- Imatinib 2 years (experimental, n = 454): Imatinib 400 mg daily for 2 years after surgery
- Observation (control, n = 454): No further therapy after surgery
- People
- Casali PG, EORTC
IFFSHR 0.79Δ 60-month IFFS+3 pointsΔ 36-month RFS+18 pointsIFFSHR 0.87Δ 60-month IFFS+4 pointsRFSHR 0.71 (95% CI 0.57–0.89)
Show the numbers
| Endpoint | Analysis | Imatinib 2 years | Observation | Effect |
|---|---|---|---|---|
| IFFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | interimmedian follow-up 4.7 yearsCasali 2015 | 87% at 5 y | 84% at 5 y | HR 0.79P=0.21The hazard ratio is published with a 98.5% confidence interval of 0.50 to 1.25 (planned interim analysis), not a 95% interval. |
| RFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | interimmedian follow-up 4.7 yearsCasali 2015 | 84% at 3 y; 69% at 5 y | 66% at 3 y; 63% at 5 y | P<0.001Log-rank P value. Secondary endpoint. 5-year overall survival 100% vs 99% in the interim analysis. |
| IFFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 87% at 5 y; 75% at 10 y | 83% at 5 y; 74% at 10 y | HR 0.87P=0.31The hazard ratio is published with a 95.7% confidence interval of 0.65 to 1.15 (adjusted for the interim analyses; IFFS assessed at a 4.3% significance level), not a 95% interval. |
| RFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 70% at 5 y; 63% at 10 y | 63% at 5 y; 61% at 10 y | HR 0.71 (95% CI 0.57–0.89)P=0.002Secondary endpoint (5% significance level). |
| OSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 93% at 5 y; 80% at 10 y | 92% at 5 y; 78% at 10 y | HR 0.88 (95% CI 0.65–1.21)P=0.43Secondary endpoint (5% significance level). |
| Endpoint | Analysis | Imatinib 2 years | Observation | Effect |
|---|---|---|---|---|
| IFFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | interimmedian follow-up 4.7 yearsCasali 2015 | 87% at 5 y | 84% at 5 y | HR 0.79P=0.21The hazard ratio is published with a 98.5% confidence interval of 0.50 to 1.25 (planned interim analysis), not a 95% interval. |
| RFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | interimmedian follow-up 4.7 yearsCasali 2015 | 84% at 3 y; 69% at 5 y | 66% at 3 y; 63% at 5 y | P<0.001Log-rank P value. Secondary endpoint. 5-year overall survival 100% vs 99% in the interim analysis. |
| IFFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 87% at 5 y; 75% at 10 y | 83% at 5 y; 74% at 10 y | HR 0.87P=0.31The hazard ratio is published with a 95.7% confidence interval of 0.65 to 1.15 (adjusted for the interim analyses; IFFS assessed at a 4.3% significance level), not a 95% interval. |
| RFSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 70% at 5 y; 63% at 10 y | 63% at 5 y; 61% at 10 y | HR 0.71 (95% CI 0.57–0.89)P=0.002Secondary endpoint (5% significance level). |
| OSRandomly assigned patients (n=908; 835 eligible); the abstract does not name the analysis population | finalmedian follow-up 9.1 yearsCasali 2021 | 93% at 5 y; 80% at 10 y | 92% at 5 y; 78% at 10 y | HR 0.88 (95% CI 0.65–1.21)P=0.43Secondary endpoint (5% significance level). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.71 | 0.57–0.89 |
| OS | 0.88 | 0.65–1.21 |
- Imatinib 2 years (experimental)
- Observation (control)
Data table (modelled values)
| Months | Imatinib 2 years | Observation |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 16 | 93.2% | 82.6% |
| 32 | 86.1% | 67.9% |
| 49 | 76.1% | 63.6% |
| 65 | 69.0% | 63.0% |
- Imatinib 2 years (experimental)
- Observation (control)
Data table (modelled values)
| Months | Imatinib 2 years | Observation |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 32 | 93.0% | 90.4% |
| 65 | 86.0% | 82.0% |
| 97 | 79.6% | 77.1% |
| 130 | 75.0% | 74.0% |
Appears in
Sources
Casali PG, Le Cesne A, Poveda Velasco A, Kotasek D, Rutkowski P, Hohenberger P, et al. Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas. J Clin Oncol. 2015;33(36):4276-83.
Casali PG, Le Cesne A, Velasco AP, Kotasek D, Rutkowski P, Hohenberger P, et al. 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), and Spanish Group for Research on Sarcomas (GEIS)(☆). Ann Oncol. 2021;32(4):533-541.