SUMMIT
A phase 2 study of bortezomib in relapsed, refractory myeloma
Phase 2N = 202
- Population
- Patients with relapsed myeloma refractory to the therapy received most recently; 193 were evaluable for response, 92 percent had been treated with three or more of the major classes of agents for myeloma and in 91 percent the myeloma was refractory to the most recent therapy.
- Design
- Multicenter, open-label, nonrandomized phase 2 trial. 202 patients with relapsed myeloma that was refractory to the most recent therapy received bortezomib 1.3 mg per square metre of body-surface area twice weekly for 2 weeks followed by 1 week without treatment, for up to eight cycles (24 weeks). Oral dexamethasone (20 mg daily, on the day of and the day after bortezomib) was added in patients with a suboptimal response. Response was evaluated by European Group for Blood and Marrow Transplantation criteria and confirmed by an independent review committee.
- Arms
- Bortezomib (experimental, n = 202): Bortezomib 1.3 mg/m2 twice weekly for 2 weeks of each 3-week cycle, up to 8 cycles; oral dexamethasone added for suboptimal response
- People
- Richardson PG
Show the numbers
| Endpoint | Analysis | Bortezomib | Control | Effect |
|---|---|---|---|---|
| ORRPatients evaluable for response (193 of 202)Rate of response by European Group for Blood and Marrow Transplantation criteria, as reported. | primaryRichardson 2003 | 35% | — | Response by European Group for Blood and Marrow Transplantation criteria, confirmed by an independent review committee; responders included 7 patients in whom myeloma protein became undetectable and 12 in whom it was detectable only by immunofixation. Grade 3 adverse events: thrombocytopenia 28%, fatigue 12%, peripheral neuropathy 12%, neutropenia 11%; grade 4 events 14%. |
| OSEnrolled patients as reported (analysis population not stated in the abstract) | primaryRichardson 2003 | median 16 months | — | — |
| DORPatients with a response (population not stated in the abstract) | primaryRichardson 2003 | median 12 months | — | — |
| OSAll SUMMIT patients (202 enrolled) | long term-updatemedian follow-up 23 monthsRichardson 2006 | median 17 months | — | Extended follow-up report of the same trial. Median overall survival was not reached in responding patients at 23 months of follow-up. |
| TTPAll SUMMIT patients (202 enrolled) | long term-updatemedian follow-up 23 monthsRichardson 2006 | median 7 months | — | Median time to progression was 13.9 months in responding patients. |
| Endpoint | Analysis | Bortezomib | Control | Effect |
|---|---|---|---|---|
| ORRPatients evaluable for response (193 of 202)Rate of response by European Group for Blood and Marrow Transplantation criteria, as reported. | primaryRichardson 2003 | 35% | — | Response by European Group for Blood and Marrow Transplantation criteria, confirmed by an independent review committee; responders included 7 patients in whom myeloma protein became undetectable and 12 in whom it was detectable only by immunofixation. Grade 3 adverse events: thrombocytopenia 28%, fatigue 12%, peripheral neuropathy 12%, neutropenia 11%; grade 4 events 14%. |
| OSEnrolled patients as reported (analysis population not stated in the abstract) | primaryRichardson 2003 | median 16 months | — | — |
| DORPatients with a response (population not stated in the abstract) | primaryRichardson 2003 | median 12 months | — | — |
| OSAll SUMMIT patients (202 enrolled) | long term-updatemedian follow-up 23 monthsRichardson 2006 | median 17 months | — | Extended follow-up report of the same trial. Median overall survival was not reached in responding patients at 23 months of follow-up. |
| TTPAll SUMMIT patients (202 enrolled) | long term-updatemedian follow-up 23 monthsRichardson 2006 | median 7 months | — | Median time to progression was 13.9 months in responding patients. |
- Bortezomib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib |
|---|---|
| 0 | 100.0% |
| 10 | 64.8% |
| 20 | 42.0% |
| 30 | 27.3% |
| 40 | 17.7% |
- Bortezomib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib |
|---|---|
| 0 | 100.0% |
| 8 | 63.0% |
| 15 | 42.0% |
| 23 | 26.5% |
| 30 | 17.7% |
Appears in
Sources
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26):2609-17.
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin DH, et al. Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma:: final time-to-event results from the SUMMIT trial. Cancer. 2006;106(6):1316-9.