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

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..

Medienart:	E-Artikel

Erscheinungsjahr:	2016
Erschienen:	2016

Enthalten in:	Zur Gesamtaufnahme - volume:17
Enthalten in:	The lancet / Oncology - 17(2016), 1, Seite 27-38

Sprache:	Englisch

Beteiligte Personen:	Dimopoulos, Meletios A. [VerfasserIn] Goldschmidt, Hartmut, 1956- [VerfasserIn]

Links:	Volltext [lizenzpflichtig] Volltext [lizenzpflichtig]

Themen:	Aged Anemia Antineoplastic Combined Chemotherapy Protocols Bortezomib Dexamethasone Disease-Free Survival Female Follow-Up Studies Humans Hypertension Male Multiple Myeloma Oligopeptides Pneumonia Retreatment Survival Rate Thrombocytopenia

Anmerkungen:	Epub 2015 Dec 5 Gesehen am 08.05.2020

Umfang:	12

doi:	10.1016/S1470-2045(15)00464-7

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1697748724