Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial
Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial
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DOI：
10.1016/s0140-6736(18)32984-2
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发表时间：
2019-01-19
期刊：
影响因子：
168.9
通讯作者：
Zinzan, Pier Luigi
中科院分区：
文献类型：
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作者：
Horwitz, Steven;O'Connor, Owen A.;Zinzan, Pier Luigi
背景基于在1期研究中观察到的令人鼓舞的活性和可管理的安全性特征，启动了ECHELON-2试验，以比较维布妥昔单抗、环磷酰胺、多柔比星和泼尼松（A+CHP）与环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）治疗CD 30阳性外周T细胞淋巴瘤的疗效和安全性。一项双模拟、随机化、安慰剂对照、活性对照药物III期研究。来自17个国家的132个研究中心的既往未经治疗的CD 30阳性外周T细胞淋巴瘤（目标为75%的系统性间变性大细胞淋巴瘤）合格成人以1：1的比例随机分配接受A+CHP或CHOP治疗，治疗6或8个21天周期。根据当地病理学评估和国际预后指数评分，按组织学亚型对随机分组进行分层。所有患者均接受环磷酰胺750 mg/m2和多柔比星50 mg/m2，每周期第1天静脉注射，泼尼松100 mg，每日1次，每周期第1 - 5天口服，随后静脉注射维布妥昔单抗1.8 mg/kg和长春新碱安慰剂（A+CHP组）或长春新碱1.4 mg/m（2）和维布妥昔单抗安慰剂静脉给药（CHOP组），每个周期第1天。主要终点，根据盲法独立中心审查的无进展生存期，通过意向治疗进行分析。该试验在www.example.com注册ClinicalTrials.gov，编号NCT 01777152。结果在2013年1月24日至2016年11月7日期间，601例患者接受了资格评估，其中452例患者入组，226例随机分配至A+CHP组和CHOP组。A+CHP组的中位无进展生存期为48.2个月（95% CI 35.2不可评估），CHOP组为20.8个月（12.7-47.6）（风险比0.71 [95% CI 0.54-0.93]，p=0.0110）。不良事件，包括发热性中性粒细胞减少症（A+CHP组41例[18%]患者，CHOP组33例[15%]患者）和周围神经病变（A+CHP组117例[52%]患者，CHOP组124例[55%]患者）的发生率和严重程度，在两组之间相似。A+CHP组7例（3%）患者和CHOP组9例（4%）患者发生致命不良事件。A+CHP一线治疗CD 30阳性外周T细胞淋巴瘤患者上级CHOP，表现为无进展生存期和总生存期显著改善，安全性可管理。版权所有（C）2018 Elsevier Ltd.保留所有权利。
Background Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.Methods ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m(2) and doxorubicin 50 mg/m(2) on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1.8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1.4 mg/m(2) and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152.Findings Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression free survival was 48.2 months (95% CI 35.2 not evaluable) in the A+CHP group and 20.8 months (12.7-47.6) in the CHOP group (hazard ratio 0.71 [95% CI 0.54-0.93], p=0.0110). Adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group.Interpretation Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile. Copyright (C) 2018 Elsevier Ltd. All rights reserved.