IV期非小细胞肺癌（NSCLC）患者的REVEL III期研究的结果表明，一种新的抗-血管生成药物，ramucirumab，和标准
“这是大约十年，在二线方案中首个用来提高患者预后的治疗，”该研究的主要作者Maurice Pérol教授（法国Lyon癌症研究中心胸部肿瘤科主任）说。“生存期的提高是显著的，因为晚期NSCLC患者在接受二线治疗方案后通常有很短的生存时间。”
Ramucirumab是一种单克隆抗体，专门靶向一种称为VEGF受体2的蛋白质，阻断肿瘤（血管生成）的新血管生长。没有其它经批准抗血管生成药物在晚期NSCLC二线治疗中可用，而且现在ramucirumab仅被批准用于晚期
晚期NSCLC二线治疗有很大的医疗需求，因为所有患者在初始治疗后最终会出现复发。已批准的晚期NSCLC二线方案包括多西他赛，
研究背景：
RAM是一种可以靶向VEGFR-2胞外域的人源IgG1单克隆抗体。该项REVEL研究针对RAM+多西他赛（DOC） vs 安慰剂（PL）+DOC两种方案治疗接受铂类为基础的治疗后的IV期非鳞状（NSQ）和鳞状（SQ）NSCLC的疗效和安全性进行评估。
研究方法：
NSQ和SQ IV期NSCLC患者按照1:1随机分配（根据性别，年龄，ECOG PS，和之前维持治疗进行分层）接受DOC 75mg/m2联合RAM 10mg/kg或者PL在为期21天周期的第1天进行，直至疾病进展，不能耐受的毒性，或者死亡。主要终点是总生存期（OS）。次要有效终点包括无进展生存期（PFS），和可观缓解率（ORR）。
研究结果：
在2010年12月和2013年2月之间，1253例患者（26.2% SQ）被随机分配（RAM+DOC组：628；DOC组：625）。患者特征在两组之间被平衡。RAM+DOC组的ORR为22.9%，DOC组为13.6%（P＜0.001）。PFS风险比（HR）值为0.762（P＜0.0001）；RAM+DOC中位PFS是4.5个月 vs DOC组3.0个月。REVEL满足它的主要终点；OS的HR值为0.857（95% CI 0.751～0.98；P=0.0235）；中位OS分别为：RAM+DOC组10.5个月 vs DOC组9.1个月。在大多数患者亚组中，包括组织病理学分型SQ和NSQ，RAM+DOC组的OS较长。
≥3级不良反应事件（AEs）发生在＞5%的RAM+DOC组患者中，是中性粒细胞减少（34.9% vs 28.0%），
研究结论：
REVEL研究证明，将RAM+DOC方案用于IV期NSCLC患者在接受铂类为基础治疗后的二线治疗，对于ORR，RFS和OS都有统计学上的显著意义。在NSQ和SQ患者中获益相似，并且确定了没有非预期的不良反应事件。临床试验信息.gov identifier: NCT01168973。
ASCO观点：
“该项研究扩展复发性或者难治性非小细胞肺癌患者的治疗选择，”Gregory A.Masters教授（ASCO专家）说。“Ramucirumab加入化疗方案中是一种有效的靶向药物，并具有低毒性。这将会带给那些在初始化疗后癌症进展的患者一个明显受益。”
医脉通整理报道，转载请注明出处。
会议专题》》》2014年ASCO年会专题报道
阅读原文摘要
REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.（Abstract #LBA8006^）
Authors: Maurice Perol, Tudor-Eliade Ciuleanu, Oscar Arrieta, et al.
Session Type: Oral Abstract Session
Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy.
Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR).
Results: Between Dec 2010 and Feb 2013, 1253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint;the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%).
Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. ClinicalTrials.gov identifier: NCT01168973.
Research Funding Source: ImClone, a wholly owned subsidiary of Eli Lilly
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