Jonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, CA 90095-1678, USA.
N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.
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.).
曲妥珠单抗可改善人表皮生长因子受体 2（HER2）阳性乳腺癌的辅助治疗中的生存率，尽管联合蒽环类药物方案治疗与心脏毒性相关。我们旨在评估曲妥珠单抗联合一种新的非蒽环类药物方案的疗效和安全性。
我们将 3222 例 HER2 阳性早期乳腺癌患者随机分配，分别接受多柔比星和环磷酰胺序贯每 3 周 1 次多西他赛（AC-T）、相同方案联合 52 周曲妥珠单抗（AC-T 加曲妥珠单抗）或多西他赛和卡铂联合 52 周曲妥珠单抗（TCH）治疗。主要研究终点为无病生存期。次要终点为总生存期和安全性。
中位随访 65 个月时，656 例事件触发了该方案规定的分析。5 年时无病生存率估计值分别为接受 AC-T 治疗的患者为 75%、接受 AC-T 加曲妥珠单抗治疗的患者为 84%、接受 TCH 治疗的患者为 81%。总生存率的估计值分别为 87%、92%和 91%。两种曲妥珠单抗方案在疗效（无病或总生存期）方面无显著差异，而两者均优于 AC-T。接受 AC-T 加曲妥珠单抗治疗的患者心力衰竭和心脏功能障碍的发生率明显高于 TCH 组（P<0.001）。报告了 8 例急性白血病：7 例发生在接受蒽环类药物方案的组，1 例发生在接受研究外蒽环类药物治疗的 TCH 组。
在 HER2 阳性乳腺癌患者中，加用 1 年的辅助曲妥珠单抗显著改善了无病生存期和总生存期。基于相似的疗效、较少的急性毒性作用、较低的心脏毒性和白血病风险，非蒽环类 TCH 方案优于 AC-T 加曲妥珠单抗方案，风险效益比有利。（由 Sanofi-Aventis 和 Genentech 资助；BCIRG-006 临床试验.gov 编号，NCT00021255。）
