Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial
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DOI：
10.1016/s0140-6736(14)60845-x
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发表时间：
2014-08-23
期刊：
影响因子：
168.9
通讯作者：
Perol, Maurice
中科院分区：
文献类型：
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作者：
Garon, Edward B.;Ciuleanu, Tudor-Eliade;Perol, Maurice
Ramucirumab是一种人IgG1单克隆抗体，靶向VEGFR-2的细胞外结构域。我们的目的是评估多西紫杉醇加ramucirumab或安慰剂作为IV期非小细胞肺癌（NSCLC）患者在铂基治疗后的二线治疗的疗效和安全性。在这项多中心、双盲、随机3期试验（REVEL）中，我们招募了在一线铂类化疗方案期间或之后发生进展的鳞状或非鳞状NSCLC患者。在21天周期的第1天，患者被随机分配（1:1）到一个集中的交互式语音应答系统（按性别、地区、表现状态和既往维持治疗分层），接受多西他赛75mg /m(2)和ramucirumab （10mg /kg）或安慰剂，直到疾病进展、不可接受的毒性、停药或死亡。主要终点是所有接受治疗的患者的总生存期。我们根据所接受的治疗评估不良事件。本研究已在ClinicalTrials.gov注册，编号NCT01168973。在2010年12月3日至2013年1月24日期间，我们筛选了1825例患者，其中1253例患者被随机分配到治疗组。628名患者中位总生存期为10.5个月（IQR 5.1-21.2）， 625名患者中位总生存期为安慰剂+多西他赛9.1个月（4.2-18.0）（风险比0.86,95% CI 0.75-0.98; p=0.023）。ramucirumab组的中位无进展生存期为4.5个月（IQR 2.3-8.3），而对照组的中位无进展生存期为3.0个月（1.4-6.9）(0.76,0.68-0.86;p
Background Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based therapy.Methods In this multicentre, double-blind, randomised phase 3 trial (REVEL), we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen. Patients were randomly allocated (1:1) with a centralised, interactive voice-response system (stratified by sex, region, performance status, and previous maintenance therapy [yes vs no]) to receive docetaxel 75 mg/m(2) and either ramucirumab (10 mg/kg) or placebo on day 1 of a 21 day cycle until disease progression, unacceptable toxicity, withdrawal, or death. The primary endpoint was overall survival in all patients allocated to treatment. We assessed adverse events according to treatment received. This study is registered with ClinicalTrials.gov, number NCT01168973.Findings Between Dec 3, 2010, and Jan 24, 2013, we screened 1825 patients, of whom 1253 patients were randomly allocated to treatment. Median overall survival was 10.5 months (IQR 5.1-21.2) for 628 patients allocated ramucirumab plus docetaxel and 9.1 months (4.2-18.0) for 625 patients who received placebo plus docetaxel (hazard ratio 0.86, 95% CI 0.75-0.98; p=0.023). Median progression-free survival was 4.5 months (IQR 2.3-8.3) for the ramucirumab group compared with 3.0 months (1.4-6.9) for the control group (0.76, 0.68-0.86; p