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

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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

ASJC Scopus subject areas

  • Oncology

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    Dimopoulos, M. A., 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., ... Chng, W. J. (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, 17(1), 27-38. https://doi.org/10.1016/S1470-2045(15)00464-7