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接受每周一次或两次卡非佐米为基础的治疗的亚洲多发性骨髓瘤患者的结局:随机 3 期 ENDEAVOR 和 A.R.R.O.W. 试验的亚组分析。

Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials.

机构信息

Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, 80 Vas Sofias Avenue, 11528, Athens, Greece.

University of Nantes, Nantes, France.

出版信息

Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.

Abstract

Carfilzomib is an irreversible proteasome inhibitor used for the treatment of relapsed and/or refractory multiple myeloma (RRMM). We evaluated the efficacy and safety of carfilzomib in subgroups of Asian patients in the randomized phase 3 ENDEAVOR and A.R.R.O.W. trials. In ENDEAVOR, patients received carfilzomib twice-weekly (56 mg/m) plus dexamethasone (Kd; n = 56) or bortezomib plus dexamethasone (Vd; n = 57). In A.R.R.O.W., patients received carfilzomib once-weekly (70 mg/m, n = 30) or twice-weekly (27 mg/m, n = 15) plus dexamethasone. Median progression-free survival (PFS) among Asian patients in ENDEAVOR was longer with Kd than with Vd (14.9 versus 8.8 months; HR 0.599); the overall response rate (ORR) was 80.4% versus 70.2%. Median overall survival (Kd versus Vd) was 47.6 versus 38.8 months (HR 0.856). Median PFS among Asian patients in A.R.R.O.W. was longer for once-weekly versus twice-weekly Kd (16.0 versus 8.4 months; HR 0.628); ORR was 76.7% versus 53.3%. Rates of grade ≥ 3 adverse events were 89.1% (Kd) and 89.5% (Vd) in ENDEAVOR, and 76.6% (once-weekly Kd) versus 73.3% (twice-weekly Kd) in A.R.R.O.W. Overall, carfilzomib had a favorable benefit-risk profile across both dosing regimens [once-weekly (Kd 70 mg/m) and twice-weekly (Kd 56 mg/m)] in Asian patients with RRMM, which was consistent with the results of both parent studies.Trial registration ClinicalTrials.gov: NCT01568866, NCT02412878.

摘要

卡非佐米是一种不可逆的蛋白酶体抑制剂,用于治疗复发和/或难治性多发性骨髓瘤(RRMM)。我们评估了卡非佐米在 ENDEAVOR 和 A.R.R.O.W. 这两项随机 3 期临床试验的亚洲患者亚组中的疗效和安全性。在 ENDEAVOR 中,患者接受卡非佐米每周 2 次(56mg/m)联合地塞米松(Kd;n=56)或硼替佐米联合地塞米松(Vd;n=57)。在 A.R.R.O.W. 中,患者接受卡非佐米每周 1 次(70mg/m,n=30)或每周 2 次(27mg/m,n=15)联合地塞米松。ENDEAVOR 中,亚洲患者的中位无进展生存期(PFS)卡非佐米 Kd 组长于硼替佐米 Vd 组(14.9 个月比 8.8 个月;HR 0.599);总缓解率(ORR)为 80.4%比 70.2%。中位总生存期(Kd 比 Vd)为 47.6 个月比 38.8 个月(HR 0.856)。A.R.R.O.W. 中,亚洲患者每周 1 次 Kd 长于每周 2 次 Kd(16.0 个月比 8.4 个月;HR 0.628);ORR 为 76.7%比 53.3%。ENDEAVOR 中,卡非佐米 Kd 组和硼替佐米 Vd 组的≥3 级不良事件发生率分别为 89.1%和 89.5%,A.R.R.O.W. 中每周 1 次 Kd 组和每周 2 次 Kd 组分别为 76.6%和 73.3%。总的来说,卡非佐米在 RRMM 亚洲患者中具有良好的获益风险比,两种剂量方案(每周 1 次[Kd 70mg/m]和每周 2 次[Kd 56mg/m])一致[1]。临床试验注册:ClinicalTrials.gov:NCT01568866,NCT02412878。

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