Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033
Phase 3N = 746NCT00009906
- Population
- Patients with metastatic or surgically unresectable GIST expressing KIT
- Design
- Open-label randomised phase III trial of standard-dose (400 mg daily) vs high-dose (400 mg twice daily) imatinib at 148 centres in the United States and Canada. On objective progression by RECIST, patients on the standard-dose arm could re-register and receive the high-dose regimen.
- Arms
- Standard dose (control): Imatinib 400 mg daily
- High dose (experimental): Imatinib 400 mg twice daily
- People
- Blanke CD
Δ median PFS+2 monthsΔ median OS−4 months
Show the numbers
| Endpoint | Analysis | High dose | Standard dose | Effect |
|---|---|---|---|---|
| PFSEnrolled patients (n=746); the abstract does not name the analysis population | primarymedian follow-up 4.5 yearsBlanke 2008 | median 20 months | median 18 months | The abstract states there were no statistically significant differences in objective response rates, progression-free survival or overall survival; no p-value or hazard ratio is given. |
| OSEnrolled patients (n=746); the abstract does not name the analysis population | primarymedian follow-up 4.5 yearsBlanke 2008 | median 51 months | median 55 months | No statistically significant difference (no p-value given in the abstract). 33% of patients who crossed over to high-dose imatinib after progression on the standard dose achieved an objective response or stable disease; more grade 3, 4 and 5 toxicities on the high-dose arm. |
| Endpoint | Analysis | High dose | Standard dose | Effect |
|---|---|---|---|---|
| PFSEnrolled patients (n=746); the abstract does not name the analysis population | primarymedian follow-up 4.5 yearsBlanke 2008 | median 20 months | median 18 months | The abstract states there were no statistically significant differences in objective response rates, progression-free survival or overall survival; no p-value or hazard ratio is given. |
| OSEnrolled patients (n=746); the abstract does not name the analysis population | primarymedian follow-up 4.5 yearsBlanke 2008 | median 51 months | median 55 months | No statistically significant difference (no p-value given in the abstract). 33% of patients who crossed over to high-dose imatinib after progression on the standard dose achieved an objective response or stable disease; more grade 3, 4 and 5 toxicities on the high-dose arm. |
- Standard dose (control)
- High dose (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard dose | High dose |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 13 | 60.6% | 63.7% |
| 25 | 38.2% | 42.0% |
| 38 | 23.1% | 26.8% |
| 50 | 14.6% | 17.7% |
- Standard dose (control)
- High dose (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard dose | High dose |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 34 | 65.1% | 63.0% |
| 69 | 41.9% | 39.1% |
| 103 | 27.3% | 24.7% |
| 138 | 17.6% | 15.3% |
Appears in
Sources
Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008;26(4):626-32.