Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial
Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial
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DOI：
10.1016/s1470-2045(15)70137-3
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发表时间：
2015-06-01
期刊：
影响因子：
51.1
通讯作者：
Hayward, Larry
中科院分区：
文献类型：
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作者：
Earl, Helena M.;Hiller, Louise;Hayward, Larry
ARTemis试验旨在评估在HER 2阴性早期乳腺癌患者的标准新辅助化疗中加入贝伐单抗的疗效和安全性。（>= 18岁）新诊断的HER 2阴性早期浸润性乳腺癌（放射学肿瘤大小>20 mm，累及或不累及腋窝）。通过中心计算机最小化程序将患者随机分配至3个多西他赛周期（100 mg/m2），每21天一次），随后是3个周期的氟尿嘧啶（500 mg/m（2）），表阿霉素（100 mg/m2）和环磷酰胺（500 mg/m2），每21天一次（D-FEC），无或有四个周期的贝伐单抗（15 mg/kg）（Bev+D-FEC）。主要终点是病理学完全缓解，定义为乳腺和腋窝淋巴结无浸润性疾病，通过意向治疗分析。试验已完成，随访正在进行中。该试验已在EudraCT（2008-002322-11）、ISRCTN（68502941）和ClinicalTrials.gov（NCT 01093235）注册。结果在2009年5月7日至2013年1月9日期间，我们将800名参与者随机分配至D-FEC组（n=401）和Bev+D-FEC组（n=399）。贝伐单抗组中达到病理学完全缓解的患者显著多于单纯化疗组：Bev+D-FEC组388例患者中有87例（22%，95% CI 18-27），而D-FEC组393例患者中有66例（17%，13-21）（p=0.03）。在两组中均报告了预期水平的3级和4级毒性，尽管Bev+D-FEC组中比D-FEC组有更多的患者具有4级中性粒细胞减少症（85 [22%]对68 [17%]）。然而，病理学完全缓解的改善是否会导致无病生存期和总生存期结局的改善尚不清楚，将在更长时间的随访后报告。现有新辅助治疗试验的荟萃分析可能是定义早期乳腺癌亚组的唯一方法，这些亚组将从贝伐单抗治疗中获得临床显著的长期获益。
Background The ARTemis trial was developed to assess the efficacy and safety of adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early breast cancer.Methods In this randomised, open-label, phase 3 trial, we enrolled women (>= 18 years) with newly diagnosed HER2-negative early invasive breast cancer (radiological tumour size >20 mm, with or without axillary involvement), at 66 centres in the UK. Patients were randomly assigned via a central computerised minimisation procedure to three cycles of docetaxel (100 mg/m(2)) once every 21 days) followed by three cycles of fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) once every 21 days (D-FEC), without or with four cycles of bevacizumab (15 mg/kg) (Bev+D-FEC). The primary endpoint was pathological complete response, defined as the absence of invasive disease in the breast and axillary lymph nodes, analysed by intention to treat. The trial has completed and follow-up is ongoing. This trial is registered with EudraCT (2008-002322-11), ISRCTN (68502941), and ClinicalTrials.gov (NCT01093235).Findings Between May 7, 2009, and Jan 9, 2013, we randomly allocated 800 participants to D-FEC (n=401) and Bev+D-FEC (n=399).781 patients were available for the primary endpoint analysis. Significantly more patients in the bevacizumab group achieved a pathological complete response compared with those treated with chemotherapy alone: 87 (22%, 95% CI 18-27) of 388 patients in the Bev+D-FEC group compared with 66 (17%, 13-21) of 393 patients in the D-FEC group (p=0.03). Grade 3 and 4 toxicities were reported at expected levels in both groups, although more patients had grade 4 neutropenia in the Bev+D-FEC group than in the D-FEC group (85 [22%] vs 68 [17%]).Interpretation Addition of four cycles of bevacizumab to D-FEC in HER2-negative early breast cancer significantly improved pathological complete response. However, whether the improvement in pathological complete response will lead to improved disease-free and overall survival outcomes is unknown and will be reported after longer follow-up. Meta-analysis of available neoadjuvant trials is likely to be the only way to define subgroups of early breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.