ROSE/TRIO-12 的主要结果，这是一项随机安慰剂对照 III 期试验，评估了在转移性乳腺癌中添加雷莫芦单抗到一线多西他赛化疗中的疗效。
Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer.
机构信息
John R. Mackey, Cross Cancer Institute; Francois Thireau and Helena Fung, Translational Research in Oncology, Edmonton; Marc Webster, Tom Baker Cancer Centre, Calgary, Alberta; Karen A. Gelmon, British Columbia Cancer Agency, Vancouver, British Columbia; Sunil Verma, Sunnybrook Health Sciences Center; Lorinda Simms, Eli Lilly, Toronto, Ontario, Canada; Manuel Ramos-Vazquez, Centro Oncológico de Galicia "José Antonio Quiroga y Piñeiro," A Coruña; Miguel Martin, Instituto de Investigación Sanitaria Gregorio Marañon, Universidad Complutense, Madrid, Spain; Oleg Lipatov, Republican Clinical Oncology Dispensary, Bashkortostan Republic Ministry of Health, Ufa; Dmitriy Krasnozhon, Leningrad Regional Oncology Dispensary, Leningrad; Vladimir Semiglazov, Institute of Oncology N.N. Petrov; Alexey Manikhas, City Clinical Oncology Dispensary, St Petersburg; Vera Gorbunova, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia; Nicole McCarthy, ICON Cancer Care Wesley, Brisbane, Queensland, Australia; Gottfried E. Konecny, University of California Los Angeles, Los Angeles, CA; Roberto Hegg, Hospital Pérola Byigton Centro de Referência da Saúde da Mulher, Sao Paulo, Brazil; Dany Abi Gerges, Middle East Institute of Health, Bsalim, Lebanon; Marc Buyse, International Drug Development Institute, Louvain-la-Neuve, Belgium; and Ayman Ibrahim, ImClone Systems, Bridgewater, NJ.
出版信息
J Clin Oncol. 2015 Jan 10;33(2):141-8. doi: 10.1200/JCO.2014.57.1513. Epub 2014 Sep 2.
PURPOSE
Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer.
PATIENTS AND METHODS
In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) -negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m(2) plus ramucirumab 10 mg/kg or docetaxel 75 mg/m(2) plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS.
RESULTS
Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio [HR], 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis.
CONCLUSION
Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes.
目的
目前，转移性乳腺癌的抗血管生成策略已显示出无进展生存期（PFS）的适度改善，但并未提高生存质量或延长生存时间，因此需要在安慰剂对照的情况下评估新药物。雷莫芦单抗是一种人免疫球蛋白 G1 抗体，可与血管内皮生长因子受体-2 结合并阻断配体刺激的激活。ROSE/TRIO-012 试验评估了雷莫芦单抗联合多西他赛治疗不可切除、局部复发或转移性乳腺癌。
患者和方法
在这项双盲、安慰剂对照、随机、多中心的 III 期临床试验中，1144 名未接受过晚期细胞毒性化疗的人表皮生长因子受体 2（HER2）阴性乳腺癌患者以 2:1 的比例随机分配，接受多西他赛 75mg/m²加雷莫芦单抗 10mg/kg 或多西他赛 75mg/m²加安慰剂，每 3 周一次。治疗继续进行，直到疾病进展、无法耐受的毒性或其他停药标准。患者按先前的紫杉烷治疗、内脏转移、激素受体状态和地理区域进行分层。一个独立的数据监测委员会监督了这项试验。主要终点是研究者评估的无进展生存期。
结果
接受雷莫芦单抗联合多西他赛治疗的患者中位无进展生存期为 9.5 个月，而接受安慰剂联合多西他赛治疗的患者为 8.2 个月（风险比 [HR]，0.88；P =.077）。接受雷莫芦单抗联合多西他赛治疗的患者中位总生存期为 27.3 个月，而接受安慰剂联合多西他赛治疗的患者为 27.2 个月（HR，1.01；P =.915）。接受雷莫芦单抗治疗的患者中，疲劳、高血压、发热性中性粒细胞减少症、掌跖红细胞感觉异常综合征和口腔炎等不良反应的发生率明显较高。
结论
在 HER2 阴性晚期乳腺癌中，雷莫芦单抗联合多西他赛并不能显著改善重要的临床结局。
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