Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study
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DOI：
10.1016/s1470-2045(15)00464-7
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发表时间：
2016-01-01
期刊：
影响因子：
51.1
通讯作者：
Chng, Wee-Joo
中科院分区：
文献类型：
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作者：
Dimopoulos, Meletios A.;Moreau, Philippe;Chng, Wee-Joo
背景：波特佐米联合地塞米松是复发性或难治性多发性骨髓瘤的标准治疗方案。卡非佐米联合地塞米松在这种疾病环境下的患者中显示出良好的活性。本研究的目的是比较卡菲佐米和地塞米松与硼替佐米和地塞米松联合治疗复发性或难治性多发性骨髓瘤患者的疗效。方法在这项随机、3期、开放、多中心研究中，复发性或难治性多发性骨髓瘤患者被随机分配(1：1)，采用分组随机方案(区组大小为4)，分别接受卡菲佐米和地塞米松治疗(卡菲佐米组)或硼替佐米联合地塞米松治疗(特佐米组)。随机分组按以前的蛋白酶体抑制剂治疗、以前的治疗路线、国际分期系统分期以及如果随机分配给地塞米松的Bortezomib的计划给药路线。患者接受卡非佐米(20 mg/m(2)在第1周期的第1天和第2天；此后56 mg/m(2)；静脉输注30分钟)、地塞米松(20 mg口服或静脉输注)或硼替佐米(1.3 mg/m(2)；静脉推注或皮下注射)和地塞米松(20 mg口服或静脉输注)的治疗，直至病情进展。主要终点是意向治疗人群中的无进展生存期。所有接受了至少一剂研究药物的参与者都被纳入了安全性分析。这项研究正在进行中，但没有招募参与者；给出了主要终点的中期分析结果。在2012年6月20日至2014年6月30日期间，929名患者被随机分配(464名患者进入carfilzomib组；465名患者进入bortezomib组)。卡非佐米组的中位随访期为11.9个月(IQR 9.3~16.1)，波特佐米组的中位随访期为11.1个月(8.2~14.3)。在预先计划的中期分析中，卡菲佐米组的中位无进展生存期为18.7个月(95%可信区间15.6-不可估计)，而波特佐米组为9.4个月(8.4-10.4)(风险比[HR]0.53[95%可信区间0.44-0.65]；p
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.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