A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)
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DOI：
10.1016/j.ejca.2022.09.037
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发表时间：
2022-11-04
影响因子：
8.4
通讯作者：
Tabernero, Josep
中科院分区：
文献类型：
--
作者：
Argiles, Guillem;Mulet, Nuria;Tabernero, Josep
目的：评价两种剂量递增治疗难治性转移性结直肠癌(MCRC)患者的安全性。患者和方法：难治性转移性结直肠癌(MCRC)患者在接受最后一次标准化疗方案后3个月或3个月内随机接受批准剂量的瑞格非尼160 mg，qd(A组)或120 mg，qd(B组)，治疗3周后停药1周，或160 mg qd，1周开始/1周结束(ARM C)。结果：299例患者随机分为A组(101例)、B组(99例)和C组(99例)；297例患者开始治疗(A组100例，B组98例，C组99例)。在A、B和C组中，与G3/4治疗相关的不良反应发生率分别为60%、55%和54%。最常见的G3/4AEs是高血压(19、12和20例)、疲劳(20、14和15例)、低钾血症(11、7和10例)和手足皮肤反应(8、7和3例)。中位总生存期A组为7.4个月(IQR 4.0~13.7)，B组为8.6个月(IQR 3.8~13.4)，C组为7.1个月(IQR 4.4~12.4)。在间歇给药组中，尤其是在相关的前两个周期中，临床上最相关的不良反应有更高的临床改善。临床试验.gov标识：NCT02835924.(C)2022年作者(S)。由爱思唯尔有限公司出版。这是一篇在CC by License(http://creativecommons.org/licenses/by/4.0/).下的开放获取文章
Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients.Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm.Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: pop-ulation for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 pa-tients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C.Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher nu-merical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924.(C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).