Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial
Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial
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DOI：
10.1200/jco.2015.64.0268
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发表时间：
2016-02-10
影响因子：
45.3
通讯作者：
Griffiths, Gareth
中科院分区：
文献类型：
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作者：
Macbeth, Fergus;Noble, Simon;Griffiths, Gareth
目的静脉血栓栓塞症(VTE)在癌症患者中很常见。有证据表明，低分子肝素(LMWH)可能通过预防VTE和转移进展来提高癌症患者的存活率。目前还没有针对单一癌症类型的试验能够证明临床上存在显著的存活率差异。这项试验的目的是在肺癌患者中调查这一问题。患者和方法我们进行了一项多中心、开放标签、随机试验，以评估在任何分期和组织学新诊断的肺癌患者的标准治疗中添加为期24周的初级预防性剂量的低分子肝素。主要结果是1年存活期。次要结果包括无转移生存期、无VTE生存期、毒性和生活质量。结果在本试验中，2202名患者被随机分配到两个治疗组，为期4年。试验没有达到初步分析的预定事件数量(2,047例死亡)，在与独立数据监测委员会讨论后，对2,013例死亡后的数据进行了分析。两组患者的总体或无转移生存率没有差异(风险比[HR]，1.01；95%CI，0.93至1.10；P=.814；HR，0.99；95%CI，0.91至1.08；P=.864)。低分子肝素组发生VTE的风险从9.7%降至5.5%(HR，0.57；95%CI，0.42至0.79；P=.001)，在主要出血事件方面没有差异，但有证据表明，低分子肝素组的主要和临床相关的非主要出血的组合增加。结论在本试验中，低分子肝素没有提高肺癌患者的总体生存率。VTE的显著减少与临床相关的非大出血的增加有关。有必要针对VTE风险最高的人群制定战略。(C)2015年度美国临床肿瘤学会
PurposeVenous thromboembolism (VTE) is common in cancer patients. Evidence has suggested that low molecular weight heparin (LMWH) might improve survival in patients with cancer by preventing both VTE and the progression of metastases. No trial in a single cancer type has been powered to demonstrate a clinically significant survival difference. The aim of this trial was to investigate this question in patients with lung cancer.Patients and MethodsWe conducted a multicenter, open-label, randomized trial to evaluate the addition of a primary prophylactic dose of LMWH for 24 weeks to standard treatment in patients with newly diagnosed lung cancer of any stage and histology. The primary outcome was 1-year survival. Secondary outcomes included metastasis-free survival, VTE-free survival, toxicity, and quality of life.ResultsFor this trial, 2,202 patients were randomly assigned to the two treatment arms over 4 years. The trial did not reach its intended number of events for the primary analysis (2,047 deaths), and data were analyzed after 2,013 deaths after discussion with the independent data monitoring committee. There was no evidence of a difference in overall or metastasis-free survival between the two arms (hazard ratio[ HR], 1.01; 95% CI, 0.93 to 1.10; P = .814; and HR, 0.99; 95% CI, 0.91 to 1.08; P = .864, respectively). There was a reduction in the risk of VTE from 9.7% to 5.5% (HR, 0.57; 95% CI, 0.42 to 0.79; P = .001) in the LMWH arm and no difference in major bleeding events but evidence of an increase in the composite of major and clinically relevant nonmajor bleeding in the LMWH arm.ConclusionLMWH did not improve overall survival in the patients with lung cancer in this trial. A significant reduction in VTE is associated with an increase in clinically relevant nonmajor bleeding. Strategies to target those at greatest risk of VTE are warranted. (C) 2015 by American Society of Clinical Oncology