Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, 80 Vas Sofias Avenue, 11528, Athens, Greece.
University of Nantes, Nantes, France.
Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.
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.
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。
