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Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
MA. Dimopoulos, P. Moreau, A. Palumbo, D. Joshua, L. Pour, R. Hájek, T. Facon, H. Ludwig, A. Oriol, H. Goldschmidt, L. Rosiñol, J. Straub, A. Suvorov, C. Araujo, E. Rimashevskaya, T. Pika, G. Gaidano, K. Weisel, V. Goranova-Marinova, A. Schwarer,...
Language English Country England, Great Britain
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 2000-09-01 to 2 months ago
Nursing & Allied Health Database (ProQuest)
from 2000-09-01 to 2 months ago
Health & Medicine (ProQuest)
from 2000-09-01 to 2 months ago
Public Health Database (ProQuest)
from 2000-09-01 to 2 months ago
- MeSH
- Anemia chemically induced MeSH
- Bortezomib administration & dosage adverse effects MeSH
- Dexamethasone administration & dosage adverse effects MeSH
- Hypertension chemically induced MeSH
- Humans MeSH
- Survival Rate MeSH
- Multiple Myeloma drug therapy MeSH
- Follow-Up Studies MeSH
- Oligopeptides administration & dosage adverse effects MeSH
- Retreatment MeSH
- Pneumonia chemically induced MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Aged MeSH
- Thrombocytopenia chemically induced MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
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/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m(2); 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<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). INTERPRETATION: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. FUNDING: Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
Alfred Health Monash University Melbourne Victoria Australia
Box Hill Hospital Box Hill Victoria Australia
Centre Hospitalier de la Cote Basque Bayonne France
CHRU Lille Hôpital Claude Huriez Lille France
Department of Hematooncology University Hospital Olomouc Olomouc Czech Republic
Heidelberg Medical University Heidelberg Germany
Hematological Department 1st Republican Clinical Hospital of Udmurtia Izhevsk Russia
Hospital Clínic de Barcelona IDIBAPS Barcelona Spain
Institut Català d'Oncologia Institut Josep Carreras Hospital Germans Trias i Pujol Barcelona Spain
Irmandade da Santa Casa de Misericórdia de Sao Paulo Sao Paulo Brazil
Kyiv Center for Bone Marrow Transplantation Kyiv Ukraine
London Health Sciences Centre Western University London Ontario Canada
Onyx Pharmaceuticals Inc an Amgen subsidiary South San Francisco CA USA
Royal Prince Alfred Hospital Camperdown New South Wales Australia
School of Medicine National and Kapodistrian University of Athens Athens Greece
Semashko Central Clinical Hospital Moscow Russia
The University of Texas MD Anderson Cancer Center The University of Texas Houston TX USA
Universitatsklinikum Tubingen Tubingen Germany
University Hospital Brno Brno Czech Republic
University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic
University of Nantes Nantes France
University of Turin Turin Italy
Vseobecna fakultni nemocnice Praha Prague Czech Republic
Wilhelminen Cancer Research Institute Wilhelminenspital Vienna Austria
References provided by Crossref.org
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- $a Dimopoulos, Meletios A $u School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: mdimop@med.uoa.gr.
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- $a 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/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m(2); 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<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). INTERPRETATION: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. FUNDING: Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
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