Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort
Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort
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DOI：
10.1016/s0140-6736(09)61964-4
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发表时间：
2010-01-01
期刊：
影响因子：
168.9
通讯作者：
Baselga, Jose
中科院分区：
文献类型：
--
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
背景单克隆抗体曲妥珠单抗与化疗联合用于HER 2（也称为ERBB 2）过表达或扩增的早期、可手术和转移性乳腺癌患者时，具有生存益处。我们的目的是评估HER 2阳性局部晚期或炎性乳腺癌患者接受新辅助化疗联合或不联合1年曲妥珠单抗治疗的无事件生存率。（作为新辅助和辅助治疗给予; n=117），无曲妥珠单抗（118），在接受新辅助化疗方案治疗的HER 2阳性局部晚期或炎性乳腺癌女性中，甲氨蝶呤和氟尿嘧啶。采用计算机程序和最小化技术进行随机化，考虑地理区域、疾病分期和激素受体状态。将治疗分配告知研究者。纳入了99例HER 2阴性疾病患者的平行队列，并接受相同的化疗方案治疗。主要终点为无事件生存期。本研究登记号为ISRCTN 86043495。结果曲妥珠单抗显著改善了HER 2阳性乳腺癌患者的无事件生存率（3年无事件生存率，曲妥珠单抗组为71% [95% CI 61-78; n=36起事件]，未曲妥珠单抗组为56% [46-65; n=51起事件];风险比0.59 [95% CI 0.38-0.90]; p=0.013）。曲妥珠单抗耐受性良好，尽管与多柔比星同时给药，但仅2例患者（2%）出现症状性心力衰竭。两者均对心脏药物有反应。解释对于HER 2阳性的局部晚期或炎性乳腺癌患者，应考虑在新辅助化疗中加入新辅助和辅助曲妥珠单抗，以提高无事件生存率、生存率以及临床和病理学的投票率反应。
Background The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.Methods We compared I year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.Findings Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61-78; n=36 events] with trastuzumab, vs 56% [46-65; n=51 events] without; hazard ratio 0.59 [95% CI 0.38-0.90]; p=0.013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.Interpretation The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological turnout responses.