APEX
Bortezomib or high-dose dexamethasone for relapsed multiple myeloma
Phase 3N = 669NCT00048230
- Population
- Patients with relapsed multiple myeloma who had received one to three previous therapies.
- Design
- Randomised comparison in 669 patients with relapsed myeloma who had received one to three previous therapies. Bortezomib 1.3 mg/m2 intravenous bolus on days 1, 4, 8 and 11 for eight three-week cycles, then days 1, 8, 15 and 22 for three five-week cycles; or high-dose dexamethasone 40 mg orally on days 1-4, 9-12 and 17-20 for four five-week cycles, then days 1-4 for five four-week cycles. Patients assigned to dexamethasone could cross over to bortezomib in a companion study after progression.
- Primary endpoint
- TTP
- Arms
- Bortezomib (experimental): Bortezomib 1.3 mg/m2 intravenous bolus, 8 three-week cycles then 3 five-week cycles
- High-dose dexamethasone (control): Dexamethasone 40 mg orally on days 1-4, 9-12 and 17-20 for 4 five-week cycles, then days 1-4 for 5 four-week cycles
- People
- Richardson PG
TTPHR 0.55Δ median TTP+2.73 monthsΔ CR+PR rate+20 pointsΔ 12-month OS+14 pointsOSHR 0.57Δ median OS+6.1 months
Show the numbers
| Endpoint | Analysis | Bortezomib | High-dose dexamethasone | Effect |
|---|---|---|---|---|
| TTPRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | median 6.22 months | median 3.49 months | HR 0.55P<0.001Time to progression was the primary end point. |
| CR+PR rateRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | 38% | 18% | P<0.001Complete response rates were 6 percent with bortezomib and less than 1 percent with dexamethasone (P<0.001). Grade 3 or 4 adverse events: 75 percent versus 60 percent. |
| OSRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | 80% at 12 mo | 66% at 12 mo | P=0.003The abstract also gives a hazard ratio for overall survival of 0.57 (P=0.001); crossover from dexamethasone to bortezomib after progression was permitted. |
| OSRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | — | — | HR 0.57P=0.001Crossover from dexamethasone to bortezomib after progression was permitted, which affects the survival comparison. |
| OSRandomised patients (updated analysis, population not stated in the abstract) | long term-updatemedian follow-up 22 monthsRichardson 2007 | median 29.8 months | median 23.7 months | Updated analysis of the same trial, reported as a 6-month benefit despite substantial crossover from dexamethasone to bortezomib. |
| ORRBortezomib arm (updated analysis) | long term-updatemedian follow-up 22 monthsRichardson 2007 | 43% | — | Complete response rate 9% in the bortezomib arm. Efficacy was updated for the bortezomib arm only; 56% of responding patients improved their response with longer therapy beyond the initial response. |
| Endpoint | Analysis | Bortezomib | High-dose dexamethasone | Effect |
|---|---|---|---|---|
| TTPRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | median 6.22 months | median 3.49 months | HR 0.55P<0.001Time to progression was the primary end point. |
| CR+PR rateRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | 38% | 18% | P<0.001Complete response rates were 6 percent with bortezomib and less than 1 percent with dexamethasone (P<0.001). Grade 3 or 4 adverse events: 75 percent versus 60 percent. |
| OSRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | 80% at 12 mo | 66% at 12 mo | P=0.003The abstract also gives a hazard ratio for overall survival of 0.57 (P=0.001); crossover from dexamethasone to bortezomib after progression was permitted. |
| OSRandomised patients (analysis population not stated in the abstract) | primaryRichardson 2005 | — | — | HR 0.57P=0.001Crossover from dexamethasone to bortezomib after progression was permitted, which affects the survival comparison. |
| OSRandomised patients (updated analysis, population not stated in the abstract) | long term-updatemedian follow-up 22 monthsRichardson 2007 | median 29.8 months | median 23.7 months | Updated analysis of the same trial, reported as a 6-month benefit despite substantial crossover from dexamethasone to bortezomib. |
| ORRBortezomib arm (updated analysis) | long term-updatemedian follow-up 22 monthsRichardson 2007 | 43% | — | Complete response rate 9% in the bortezomib arm. Efficacy was updated for the bortezomib arm only; 56% of responding patients improved their response with longer therapy beyond the initial response. |
- Bortezomib (experimental)
- High-dose dexamethasone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib | High-dose dexamethasone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 4 | 64.0% | 45.2% |
| 8 | 41.0% | 20.4% |
| 12 | 26.3% | 9.2% |
| 16 | 16.8% | 4.2% |
- Bortezomib (experimental)
- High-dose dexamethasone (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Bortezomib | High-dose dexamethasone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 19 | 64.3% | 57.4% |
| 37 | 42.3% | 33.9% |
| 56 | 27.2% | 19.4% |
| 75 | 17.5% | 11.2% |
Appears in
Sources
Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487-98.
Richardson PG, Sonneveld P, Schuster M, Irwin D, Stadtmauer E, Facon T, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007;110(10):3557-60.