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ENDEAVOR

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR)

Phase 3N = 929NCT01568866

Population
Relapsed or refractory multiple myeloma after one to three previous treatments.
Design
Randomised, phase 3, open-label, multicentre study: 929 patients with one to three previous treatments were randomly assigned 1:1 to carfilzomib with dexamethasone or bortezomib with dexamethasone until progression. The primary end point was progression-free survival in the intention-to-treat population; results are from a preplanned interim analysis.
Primary endpoint
PFS
Arms
  • Carfilzomib + dexamethasone (experimental, n = 464): Carfilzomib 20 mg/m2 on days 1 and 2 of cycle 1 then 56 mg/m2 with dexamethasone 20 mg
  • Bortezomib + dexamethasone (control, n = 465): Bortezomib 1.3 mg/m2 with dexamethasone 20 mg
People
Dimopoulos MA
PFSHR 0.53 (95% CI 0.44–0.65)Δ median PFS+9.3 months
Show the numbers
Results reported for ENDEAVOR
EndpointAnalysisCarfilzomib + dexamethasoneBortezomib + dexamethasoneEffect
PFSITT population (929)interimDimopoulos 2016median 18.7 monthsmedian 9.4 months (8.4–10.4)HR 0.53 (95% CI 0.44–0.65)P<0.0001Median follow-up was 11.9 months (IQR 9.3 to 16.1) with carfilzomib and 11.1 months (8.2 to 14.3) with bortezomib. The 95% CI of the carfilzomib median is 15.6 months to not estimable (lower bound only). On-study death due to adverse events occurred in 18 (4%) and 16 (3%) patients; serious adverse events in 224 (48%) and 162 (36%); grade 3 or higher hypertension in 41 (9%) and 12 (3%).
Results reported for ENDEAVOR
EndpointAnalysisCarfilzomib + dexamethasoneBortezomib + dexamethasoneEffect
PFSITT population (929)interimDimopoulos 2016median 18.7 monthsmedian 9.4 months (8.4–10.4)HR 0.53 (95% CI 0.44–0.65)P<0.0001Median follow-up was 11.9 months (IQR 9.3 to 16.1) with carfilzomib and 11.1 months (8.2 to 14.3) with bortezomib. The 95% CI of the carfilzomib median is 15.6 months to not estimable (lower bound only). On-study death due to adverse events occurred in 18 (4%) and 16 (3%) patients; serious adverse events in 224 (48%) and 162 (36%); grade 3 or higher hypertension in 41 (9%) and 12 (3%).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.530.44–0.65
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%010203040Months (modelled)
  • Carfilzomib + dexamethasone (experimental)
  • Bortezomib + dexamethasone (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsCarfilzomib + dexamethasoneBortezomib + dexamethasone
0100.0%100.0%
1264.1%41.3%
2342.6%18.3%
3527.3%7.6%
4717.5%3.1%
Primary publication: Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38. PubMedDOI

Appears in

Sources

  1. Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38.

    PubMedDOI