Bevacizumab added to neoadjuvant chemotherapy for breast cancer.
Bevacizumab added to neoadjuvant chemotherapy for breast cancer.
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DOI：
10.1056/nejmoa1111097
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发表时间：
2012-01-26
期刊：
影响因子：
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通讯作者：
Wolmark N
中科院分区：
文献类型：
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作者：
Bear HD;Tang G;Rastogi P;Geyer CE Jr;Robidoux A;Atkins JN;Baez-Diaz L;Brufsky AM;Mehta RS;Fehrenbacher L;Young JA;Senecal FM;Gaur R;Margolese RG;Adams PT;Gross HM;Costantino JP;Swain SM;Mamounas EP;Wolmark N
贝伐珠单抗和抗代谢药物卡培他滨和吉西他滨已被证明添加到紫杉烷类药物中可以改善转移性乳腺癌患者的预后。该试验的主要目的是确定在多西紫杉醇新辅助化疗中添加卡培他滨或吉西他滨，然后添加阿霉素加环磷酰胺是否会增加可手术的人表皮生长因子受体 2 (HER2) 阴性乳腺癌女性乳房病理完全缓解率，以及在这些化疗方案中添加贝伐珠单抗是否会增加乳腺癌的病理完全缓解率。 病理完全反应。我们随机分配 1206 名患者接受新辅助治疗，包括多西他赛（第 1 天每平方米体表面积 100 mg）、多西他赛（第 1 天每平方米体表面积 75 mg）加卡培他滨（第 1 至 14 天每平方米 825 mg）或多西他赛（第 1 天每平方米体表面积 75 mg）加吉西他滨（第 1 天每平方米 1000 mg）。 第 1 天和第 8 天）共四个周期，所有方案均随后用阿霉素-环磷酰胺治疗四个周期。在前六个化疗周期中，患者还被随机分配接受或不接受贝伐单抗（每公斤体重 15 毫克）。与单独使用多西紫杉醇治疗相比，在多西紫杉醇治疗中加入卡培他滨或吉西他滨并没有显着提高病理完全缓解率（分别为 29.7% 和 31.8% vs. 32.7%；P = 0.69）。卡培他滨和吉西他滨都与毒性作用增加有关，特别是手足综合征、粘膜炎和中性粒细胞减少症。添加贝伐单抗显着提高了病理完全缓解率（无贝伐单抗为 28.2%，而贝伐单抗为 34.5%，P = 0.02）。贝伐珠单抗对病理完全缓解率的影响在激素受体阳性和激素受体阴性亚组中并不相同。添加贝伐珠单抗会增加高血压、左心室收缩功能障碍、手足综合征和粘膜炎的发生率。新辅助化疗中添加贝伐单抗显着提高了病理完全缓解率，这是本研究的主要终点。 （由国家癌症研究所和其他机构资助；ClinicalTrials.gov 编号，NCT00408408。）
Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)–negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response. We randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin–cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy. The addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P = 0.69). Both capecitabine and gemcitabine were associated with increased toxic effects — specifically, the hand–foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P = 0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor–positive and hormone-receptor–negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand–foot syndrome, and mucositis. The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.)