贝伐珠单抗联合新辅助化疗治疗乳腺癌。
Bevacizumab added to neoadjuvant chemotherapy for breast cancer.
机构信息
Medical College of Virginia School of Medicine and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298-0011, USA.
出版信息
N Engl J Med. 2012 Jan 26;366(4):310-20. doi: 10.1056/NEJMoa1111097.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.).
背景
贝伐单抗以及抗代谢药物卡培他滨和吉西他滨与紫杉醇联合应用于转移性乳腺癌患者时，可改善患者的预后。本试验的主要目的是确定在可手术的人表皮生长因子受体 2（HER2）阴性乳腺癌患者中，与多西他赛、多柔比星和环磷酰胺辅助化疗相比，添加卡培他滨或吉西他滨是否会增加病理完全缓解的发生率，以及添加贝伐单抗是否会增加这些化疗方案的病理完全缓解率。
方法
我们将 1206 名患者随机分配接受新辅助治疗，方案为多西他赛（100mg/m²，第 1 天）、多西他赛（75mg/m²，第 1 天）联合卡培他滨（825mg，每天 2 次，第 1-14 天）或多西他赛（75mg/m²，第 1 天）联合吉西他滨（1000mg/m²，第 1 和 8 天），共 4 个周期，所有方案均随后接受多柔比星-环磷酰胺 4 个周期的治疗。患者还被随机分配接受或不接受贝伐单抗（15mg/kg），用于前 6 个周期的化疗。
结果
与单纯多西他赛治疗相比，卡培他滨或吉西他滨联合多西他赛治疗并未显著提高病理完全缓解率（分别为 29.7%和 31.8%，32.7%；P=0.69）。卡培他滨和吉西他滨均与更多的毒副作用相关，特别是手足综合征、黏膜炎和中性粒细胞减少症。贝伐单抗的加入显著提高了病理完全缓解率（无贝伐单抗组为 28.2%，有贝伐单抗组为 34.5%，P=0.02）。贝伐单抗对病理完全缓解率的影响在激素受体阳性和阴性亚组中并不相同。贝伐单抗的加入增加了高血压、左心室收缩功能障碍、手足综合征和黏膜炎的发生率。
结论
贝伐单抗联合新辅助化疗显著提高了病理完全缓解率，这是本研究的主要终点。（由美国国立癌症研究所等资助；ClinicalTrials.gov 编号，NCT00408408。）
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