柳叶刀：新药Cyramza或可有效延长非小细胞肺癌患者的生存期

  近日，美国FDA批准了一种新药用于治疗非小细胞肺癌（NSCLC），其就为患NSCLC的病人治疗疾病带来了巨大帮助，每年仅在美国就有超过15万人死于肺癌，而NSCLC在所有的肺癌中占到了85%。目前这种名为Cyramza的新药已经在超过1200名正在进行第一阶段或已经进行完第一阶段化疗的NSCLC患者中完成了检测。
  来自加州大学洛杉矶分校的研究人员表示，这项研究其中有一部分他们已经进行了多年的研究，目前已经进行到了3期临床阶段研究，而本文研究中研究者发现，药物Cyramza可以明显延长肺癌患者的生存期。Cyramza是一种可以靶向作用VEGFR-2胞外结构域的抗体，VEGFR-2是在机体血管中形成的一种蛋白，其可以向癌细胞供给血液。
  当患者疾病恶化后通常的标准化疗法就是利用单一药物对患者进行化疗，通常患者的总体生存期仅为7个月，而且仅有将近10%的患者对化疗产生反应。然而当研究者将新药Cyramza同多西紫杉醇联合后用于治疗肺癌恶化的病人后就观察到了病人明显的有益性表现，其中研究者观察到23%的病人都对药物产生了反应，这就意味着利用联合疗法进行治疗后患者机体的肿瘤会发生明显的缩小。
  研究者Garon表示，将Cyramza同多西紫杉醇结合后作为标准疗法来治疗肺癌患者可以明显延长患者的寿命，尽管患者会出现一定的副作用，但大部分副作用都是常见的嗜中性白血球减少症、疲劳及高血压；未来研究人员将会对Cyramza药物同其它药物联合治疗肺癌进行评估，研究者希望可以找到更加有效抑制肺癌患者疾病恶化的药物组合。（转化医学网360zhyx.com）
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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
The Lancet doi:10.1016/S0140-6736(14)60845-X
Dr Edward B Garon, MD, Prof Tudor-Eliade Ciuleanu, MD, Oscar Arrieta, MD, Prof Kumar Prabhash, MD, Prof Konstantinos N Syrigos, MD, Prof Tuncay Goksel, MD, Prof Keunchil Park, MD, Vera Gorbunova, MD, Ruben Dario Kowalyszyn, MD, Joanna Pikiel, MD, Grzegorz Czyzewicz, MD, Prof Sergey V Orlov, MD, Conrad R Lewanski, MD, Prof Michael Thomas, MD, Paolo Bidoli, MD, Shaker Dakhil, MD, Steven Gans, MD, Prof Joo-Hang Kim, MD, Prof Alexandru Grigorescu, MD, Nina Karaseva, MD, Martin Reck, MD, Federico Cappuzzo, MD, Ekaterine Alexandris, MS, Andreas Sashegyi, PhD, Sergey Yurasov, MD, Maurice Pérol, MD
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/m2 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<0·0001). We noted treatment-emergent adverse events in 613 (98%) of 627 patients in the ramucirumab safety population and 594 (95%) of 618 patients in the control safety population. The most common grade 3 or worse adverse events were neutropenia (306 patients [49%] in the ramucirumab group vs 246 [40%] in the control group), febrile neutropenia (100 [16%] vs 62 [10%]), fatigue (88 [14%] vs 65 [10%]), leucopenia (86 [14%] vs 77 [12%]), and hypertension (35 [6%] vs 13 [2%]). The numbers of deaths from adverse events (31 [5%] vs 35 [6%]) and grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight [1%]) did not differ between groups. Toxicities were manageable with appropriate dose reductions and supportive care.
Interpretation
Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC.
Funding
Eli Lilly.