曲妥珠单抗联合辅助化疗用于人表皮生长因子受体2阳性乳腺癌：NSABP B-31和NCCTG N9831总生存的计划联合分析
Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831.
作者信息
Perez Edith A, Romond Edward H, Suman Vera J, Jeong Jong-Hyeon, Sledge George, Geyer Charles E, Martino Silvana, Rastogi Priya, Gralow Julie, Swain Sandra M, Winer Eric P, Colon-Otero Gerardo, Davidson Nancy E, Mamounas Eleftherios, Zujewski Jo Anne, Wolmark Norman
机构信息
Edith A. Perez, Gerardo Colon-Otero, the Mayo Clinic, Jacksonville; Eleftherios Mamounas, University of Florida Health Cancer Center-Orlando Health, Orlando, FL; Edward H. Romond, University of Kentucky, Lexington, KY; Vera J. Suman, Mayo Clinic, Rochester, MN; Jong-Hyeon Jeong, Priya Rastogi, University of Pittsburgh; Nancy E. Davidson, University of Pittsburgh Cancer Institute; Norman Wolmark, Allegheny General Hospital, Pittsburgh, PA; George Sledge, Stanford University School of Medicine, Stanford; Silvana Martino, The Angeles Clinic and Research Institute, Santa Monica, CA; Charles E. Geyer Jr, Virginia Commonwealth University Massey Cancer Center, Richmond, VA; Julie Gralow, University of Washington/Seattle Cancer Care Alliance, Seattle, WA; Sandra M. Swain, MedStar Washington Hospital Center, Washington, DC; Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jo Anne Zujewski, National Institutes of Health, Rockville, MD.
出版信息
J Clin Oncol. 2014 Nov 20;32(33):3744-52. doi: 10.1200/JCO.2014.55.5730. Epub 2014 Oct 20.
PURPOSE
Positive interim analysis findings from four large adjuvant trials evaluating trastuzumab in patients with early-stage human epidermal growth factor receptor 2 (HER2) -positive breast cancer were first reported in 2005. One of these reports, the joint analysis of North Central Cancer Treatment Group NCCTG N9831 (Combination Chemotherapy With or Without Trastuzumab in Treating Women With HER2-Overexpressing Breast Cancer) and the National Surgical Adjuvant Breast and Bowel Project NSABP B-31 (Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2), was updated in 2011. We now report the planned definitive overall survival (OS) results from this joint analysis along with updates on the disease-free survival (DFS) end point.
METHODS
In all, 4,046 patients with HER2-positive operable breast cancer were enrolled to receive doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in both trials. The required number of events for the definitive statistical analysis for OS (710 events) was reached in September 2012. Updated analyses of overall DFS and related subgroups were also performed.
RESULTS
Median time on study was 8.4 years. Adding trastuzumab to chemotherapy led to a 37% relative improvement in OS (hazard ratio [HR], 0.63; 95% CI, 0.54 to 0.73; P < .001) and an increase in 10-year OS rate from 75.2% to 84%. These results were accompanied by an improvement in DFS of 40% (HR, 0.60; 95% CI, 0.53 to 0.68; P < .001) and increase in 10-year DFS rate from 62.2% to 73.7%. All patient subgroups benefited from addition of this targeted anti-HER2 agent.
CONCLUSION
The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence.
目的
2005年首次报告了四项评估曲妥珠单抗用于早期人表皮生长因子受体2（HER2）阳性乳腺癌患者的大型辅助试验的阳性中期分析结果。其中一份报告，即北中部癌症治疗组NCCTG N9831（HER2过表达乳腺癌女性患者联合化疗加或不加曲妥珠单抗）与国家外科辅助乳腺和肠道项目NSABP B - 31（阿霉素和环磷酰胺加紫杉醇加或不加曲妥珠单抗治疗HER2过表达的淋巴结阳性乳腺癌女性患者）的联合分析，于2011年进行了更新。我们现在报告该联合分析的计划最终总生存（OS）结果以及无病生存（DFS）终点的更新情况。
方法
两项试验共纳入4046例HER2阳性可手术乳腺癌患者，接受阿霉素和环磷酰胺治疗，随后接受紫杉醇治疗，部分患者加用曲妥珠单抗。2012年9月达到了OS最终统计分析所需的事件数（710个事件）。还对总体DFS及相关亚组进行了更新分析。
结果
研究的中位时间为8.4年。化疗中加用曲妥珠单抗使OS相对改善37%（风险比[HR]，0.63；95%可信区间[CI]，0.54至0.73；P <.001），10年OS率从75.2%提高到84%。这些结果伴随着DFS改善40%（HR，0.60；95%CI，0.53至0.68；P <.001），10年DFS率从62.2%提高到73.7%。所有患者亚组均从添加这种靶向抗HER2药物中获益。
结论
在早期HER2阳性乳腺癌患者中，在阿霉素和环磷酰胺之后加用曲妥珠单抗至紫杉醇治疗，由于癌症复发持续显著减少，可导致生存的实质性和持久性改善。
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