Adjuvant trastuzumab in HER2-positive breast cancer.
Adjuvant trastuzumab in HER2-positive breast cancer.
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DOI：
10.1056/nejmoa0910383
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发表时间：
2011-10-06
期刊：
影响因子：
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通讯作者：
Breast Cancer International Research Group
中科院分区：
文献类型：
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作者：
Slamon D;Eiermann W;Robert N;Pienkowski T;Martin M;Press M;Mackey J;Glaspy J;Chan A;Pawlicki M;Pinter T;Valero V;Liu MC;Sauter G;von Minckwitz G;Visco F;Bee V;Buyse M;Bendahmane B;Tabah-Fisch I;Lindsay MA;Riva A;Crown J;Breast Cancer International Research Group
曲妥珠单抗可提高 HER 阳性乳腺癌辅助治疗的生存率，尽管与基于蒽环类药物的方案联合治疗与心脏毒性有关。我们想要评估新的非蒽环类药物曲妥珠单抗治疗方案的有效性和安全性。我们随机分配 3222 名 HER2 阳性早期乳腺癌女性接受多柔比星和环磷酰胺治疗，随后每 3 周接受多西他赛治疗 (AC-T)、相同方案加 52 周曲妥珠单抗治疗（AC-T 加曲妥珠单抗），或多西他赛和卡铂加 52 周曲妥珠单抗治疗 (TCH)。主要研究终点是无病生存期。次要终点是总体生存率和安全性。在中位随访 65 个月中，656 个事件触发了该方案指定的分析。接受 AC-T 的患者估计 5 年无病生存率为 75%，接受 AC-T 加曲妥珠单抗的患者为 84%，接受 TCH 的患者为 81%。估计总生存率分别为 87%、92% 和 91%。两种曲妥珠单抗方案之间没有发现疗效（无病生存或总生存）存在显着差异，但均优于 AC-T。 AC-T联合曲妥珠单抗组的充血性心力衰竭和心功能不全发生率显着高于TCH组（P<0.001）。报告了 8 例急性白血病病例：接受基于蒽环类药物治疗的组中有 7 例，TCH 组中有 1 例是在研究之外接受蒽环类药物后发生的。添加 1 年曲妥珠单抗辅助治疗可显着改善 HER2 阳性乳腺癌女性的无病生存率和总生存率。考虑到非蒽环类 TCH 方案与 AC-T 加曲妥珠单抗相似的疗效、较少的急性毒性作用以及较低的心脏毒性和白血病风险，风险效益比更倾向于非蒽环类 TCH 方案。 （由赛诺菲-安万特和基因泰克资助；BCIRG-006 ClinicalTrials.gov 编号，NCT00021255。）
Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab. We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety. At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study. The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.)