在早期乳腺癌研究中，多西他赛＋环磷酰胺（TC）优于多柔比星＋环磷酰胺（AC）。然而，TC相比TAC方案（TaxAC）的活性尚不明确。
2017年4月11日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表美国肿瘤学研究（USOR）、麦克森专业医疗、德克萨斯肿瘤学、贝勒查尔斯萨蒙斯癌症中心、贝勒大学医学中心、NRG（NSABP、RTOG、GOG）肿瘤学、匹兹堡大学、阿勒格尼综合医院、东部肿瘤学协作组与美国放射学会成像网络（ECOG-ACRIN）、明尼苏达社区肿瘤研究联盟、弗吉尼亚联邦大学、弗吉尼亚癌症专科医生、东南肿瘤医学中心、联盟、纪念斯隆凯特琳癌症中心、秘鲁国家肿瘤学研究所、北加利福尼亚凯泽永久肿瘤学临床研究中心、密苏里浸信会癌症中心、洛矶山癌症中心、华盛顿医院中心、乔治城大学、佛罗里达大学的研究报告，对蒽环类药物加入TC方案用于早期乳腺癌的三项辅助疗法系列研究进行了联合分析。
三项辅助疗法系列研究（USOR 06-090、NSABP B-46-I/USOR 07132、NSABP B-49）将4242例HER2阴性早期乳腺癌女性随机分组接受6个周期TC（TC6）或标准TaxAC方案。其中：
USOR 06-090比较了TC6与多西他赛＋多柔比星＋环磷酰胺（TAC6）
NSABP B-46-I/USOR 07132比较了TC6、TAC6或TC6＋贝伐珠单抗
NSABP B-49比较了TC6与若干标准的AC＋紫杉类联合方案
在对个别研究进行任何分析之前，计划对TC比较TaxAC方案进行联合有效性分析，将无浸润性病变生存（IDFS）作为主要终点。在NSABP B-46-I/USOR 07132研究中接受TC6＋贝伐单抗的患者被剔除。通过分层比例风险（Cox）模型，TC6与TaxAC的风险比＞1.18被预先定义为TaxAC优于TC6。若观察到334个IDFS事件（确定性分析所需668个事件中的50%）时风险比＞1.18，则可按预先规定的中期监测计划进行报告。
结果发现，随机分配接受TC6方案、TaxAC方案的患者分别为2125、2117例。中位随访时间为3.3年。当334个IDFS事件发生时，TC6与TaxAC的风险比为1.202（95%置信区间：0.97～1.49）。TC6、TaxAC的4年IDFS分别为88.2%、90.7%（P=0.04）。根据方案、激素受体状态、淋巴结状态，对治疗方案进行相互影响检验，结果均为阴性。
因此，TaxAC方案与TC6方案相比，改善了高风险HER2阴性乳腺癌患者的IDFS。
J Clin Oncol. 2017 Apr 11. [Epub ahead of print]
Anthracyclines in Early Breast Cancer: The ABC Trials--USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology).
Joanne L. Blum, Patrick J. Flynn, Greg Yothers, Lina Asmar, Charles E. Geyer, Samuel A. Jacobs, Nicholas J. Robert, Judith O. Hopkins, Joyce A. O'Shaughnessy, Chau T. Dang, Henry Leonidas Gómez, Louis Fehrenbacher, Svetislava J. Vukelja, Alan P. Lyss, Devchand Paul, Adam M. Brufsky, Jong-Hyeon Jeong, Linda H. Colangelo, Sandra M. Swain, Eleftherios P. Mamounas, Stephen E. Jones, Norman Wolmark.
US Oncology Research; McKesson Specialty Health, The Woodlands; Texas Oncology-Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas; Texas Oncology-Tyler, Tyler, TX; National Surgical Adjuvant Breast and Bowel Project/NRG Oncology; NRG Oncology; The University of Pittsburgh; University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine; Magee-Womens Hospital at University of Pittsburgh Medical Center; Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh; Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Philadelphia, PA; Metro-Minnesota Community Oncology Research Consortium, Minneapolis, MN; Massey Cancer Center, Virginia Commonwealth University, Richmond; Virginia Cancer Specialists, Fairfax, VA; The Southeastern Medical Oncology Center, Goldsboro, NC; The Alliance, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru; Kaiser Permanente Oncology Clinical Trials Northern California, Vallejo, CA; Heartland Cancer Research National Cancer Institute Community Oncology Research Program at Missouri Baptist Cancer Center, St Louis, MO; Rocky Mountain Cancer Centers, Denver, CO; MedStar Washington Hospital Center Washington Cancer Institute, Georgetown University Medical Center, Washington, DC; UF Cancer Center at Orlando Health, Orlando, FL.
PURPOSE: Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown.
METHODS: In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis).
RESULTS: A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC (P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative.
CONCLUSION: The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer compared with the TC6 regimen.
DOI: 10.1200/JCO.2016.71.4147
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