Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Meletios A. Dimopoulos, Philippe Moreau, Antonio Palumbo, Douglas Joshua, Ludek Pour, Roman Hájek, Thierry Facon, Heinz Ludwig, Albert Oriol, Hartmut Goldschmidt, Laura Rosiñol, Jan Straub, Aleksandr Suvorov, Carla Araujo, Elena Rimashevskaya, Tomas Pika, Gianluca Gaidano, Katja Weisel, Vesselina Goranova-Marinova, Anthony SchwarerLeonard Minuk, T. Masszi, Ievgenii Karamanesht, Massimo Offidani, Vania Hungria, Andrew Spencer, Robert Z. Orlowski, Heidi H. Gillenwater, Nehal Mohamed, Shibao Feng, Wee Joo Chng

Research output: Article

342 Citations (Scopus)

Abstract

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p

Original languageEnglish
Pages (from-to)27-38
Number of pages12
JournalThe Lancet Oncology
Volume17
Issue number1
DOIs
Publication statusPublished - jan. 1 2016

Fingerprint

Multiple Myeloma
Dexamethasone
Multicenter Studies
Intravenous Infusions
Random Allocation
Disease-Free Survival
Bortezomib
carfilzomib
Therapeutics
Proteasome Inhibitors
Subcutaneous Injections
Intravenous Injections
Safety

ASJC Scopus subject areas

  • Oncology

Cite this

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR) : And randomised, phase 3, open-label, multicentre study. / Dimopoulos, Meletios A.; Moreau, Philippe; Palumbo, Antonio; Joshua, Douglas; Pour, Ludek; Hájek, Roman; Facon, Thierry; Ludwig, Heinz; Oriol, Albert; Goldschmidt, Hartmut; Rosiñol, Laura; Straub, Jan; Suvorov, Aleksandr; Araujo, Carla; Rimashevskaya, Elena; Pika, Tomas; Gaidano, Gianluca; Weisel, Katja; Goranova-Marinova, Vesselina; Schwarer, Anthony; Minuk, Leonard; Masszi, T.; Karamanesht, Ievgenii; Offidani, Massimo; Hungria, Vania; Spencer, Andrew; Orlowski, Robert Z.; Gillenwater, Heidi H.; Mohamed, Nehal; Feng, Shibao; Chng, Wee Joo.

In: The Lancet Oncology, Vol. 17, No. 1, 01.01.2016, p. 27-38.

Research output: Article

Dimopoulos, MA, Moreau, P, Palumbo, A, Joshua, D, Pour, L, Hájek, R, Facon, T, Ludwig, H, Oriol, A, Goldschmidt, H, Rosiñol, L, Straub, J, Suvorov, A, Araujo, C, Rimashevskaya, E, Pika, T, Gaidano, G, Weisel, K, Goranova-Marinova, V, Schwarer, A, Minuk, L, Masszi, T, Karamanesht, I, Offidani, M, Hungria, V, Spencer, A, Orlowski, RZ, Gillenwater, HH, Mohamed, N, Feng, S & Chng, WJ 2016, 'Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study', The Lancet Oncology, vol. 17, no. 1, pp. 27-38. https://doi.org/10.1016/S1470-2045(15)00464-7
Dimopoulos, Meletios A. ; Moreau, Philippe ; Palumbo, Antonio ; Joshua, Douglas ; Pour, Ludek ; Hájek, Roman ; Facon, Thierry ; Ludwig, Heinz ; Oriol, Albert ; Goldschmidt, Hartmut ; Rosiñol, Laura ; Straub, Jan ; Suvorov, Aleksandr ; Araujo, Carla ; Rimashevskaya, Elena ; Pika, Tomas ; Gaidano, Gianluca ; Weisel, Katja ; Goranova-Marinova, Vesselina ; Schwarer, Anthony ; Minuk, Leonard ; Masszi, T. ; Karamanesht, Ievgenii ; Offidani, Massimo ; Hungria, Vania ; Spencer, Andrew ; Orlowski, Robert Z. ; Gillenwater, Heidi H. ; Mohamed, Nehal ; Feng, Shibao ; Chng, Wee Joo. / Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR) : And randomised, phase 3, open-label, multicentre study. In: The Lancet Oncology. 2016 ; Vol. 17, No. 1. pp. 27-38.
@article{0ffce3a8566f47c1a1eba8b8a91c58d6,
title = "Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study",
abstract = "Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95{\%} CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95{\%} CI 0·44-0·65]; p",
author = "Dimopoulos, {Meletios A.} and Philippe Moreau and Antonio Palumbo and Douglas Joshua and Ludek Pour and Roman H{\'a}jek and Thierry Facon and Heinz Ludwig and Albert Oriol and Hartmut Goldschmidt and Laura Rosi{\~n}ol and Jan Straub and Aleksandr Suvorov and Carla Araujo and Elena Rimashevskaya and Tomas Pika and Gianluca Gaidano and Katja Weisel and Vesselina Goranova-Marinova and Anthony Schwarer and Leonard Minuk and T. Masszi and Ievgenii Karamanesht and Massimo Offidani and Vania Hungria and Andrew Spencer and Orlowski, {Robert Z.} and Gillenwater, {Heidi H.} and Nehal Mohamed and Shibao Feng and Chng, {Wee Joo}",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/S1470-2045(15)00464-7",
language = "English",
volume = "17",
pages = "27--38",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "1",

}

TY - JOUR

T1 - Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR)

T2 - And randomised, phase 3, open-label, multicentre study

AU - Dimopoulos, Meletios A.

AU - Moreau, Philippe

AU - Palumbo, Antonio

AU - Joshua, Douglas

AU - Pour, Ludek

AU - Hájek, Roman

AU - Facon, Thierry

AU - Ludwig, Heinz

AU - Oriol, Albert

AU - Goldschmidt, Hartmut

AU - Rosiñol, Laura

AU - Straub, Jan

AU - Suvorov, Aleksandr

AU - Araujo, Carla

AU - Rimashevskaya, Elena

AU - Pika, Tomas

AU - Gaidano, Gianluca

AU - Weisel, Katja

AU - Goranova-Marinova, Vesselina

AU - Schwarer, Anthony

AU - Minuk, Leonard

AU - Masszi, T.

AU - Karamanesht, Ievgenii

AU - Offidani, Massimo

AU - Hungria, Vania

AU - Spencer, Andrew

AU - Orlowski, Robert Z.

AU - Gillenwater, Heidi H.

AU - Mohamed, Nehal

AU - Feng, Shibao

AU - Chng, Wee Joo

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p

AB - Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p

UR - http://www.scopus.com/inward/record.url?scp=84955420512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955420512&partnerID=8YFLogxK

U2 - 10.1016/S1470-2045(15)00464-7

DO - 10.1016/S1470-2045(15)00464-7

M3 - Article

C2 - 26671818

AN - SCOPUS:84955420512

VL - 17

SP - 27

EP - 38

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 1

ER -