新英格兰翻了圣安东尼奥哪块牌子

　　每年12月，全球规模最大的乳腺癌学术会议在美国德克萨斯圣安东尼奥召开，2018年为第41届。期间，最重要的乳腺癌研究全文，通常将被国际学术期刊影响因子排名第二、世界四大医学期刊之首、已有190年历史的美国麻省医学会《新英格兰医学杂志》同步发表。

　　对于HER2阳性早期乳腺癌患者，术前新辅助化疗＋曲妥珠单抗HER2靶向治疗后，残留与未残留浸润病变的患者相比，预后较差。曲妥珠单抗-恩坦辛（T-DM1，又称恩特曲妥珠单抗、恩星曲妥珠单抗）由单克隆抗体与细胞毒性药物恩坦辛（DM1，美坦辛衍生物，属于细胞有丝分裂微管抑制剂）结合而成，根据2012年11月发表于《新英格兰医学杂志》的EMILIA研究结果，T-DM1二线治疗可以显著改善HER2阳性晚期乳腺癌患者的无进展生存和总生存，故于2013年2月获得美国食品药品监督管理局（FDA）批准上市用于二线治疗HER2阳性晚期乳腺癌。不过，T-DM1至今未获中国大陆内地批准。

　　2018年12月5日，美国麻省医学会《新英格兰医学杂志》在线发表德国乳腺癌研究组织（GBG）、法兰克福大学、德国妇科肿瘤学会（AGO）乳腺癌学组、柏林大学、海德堡大学、德国癌症研究中心、国家肿瘤疾病中心、盖尔森基兴大学、奥芬巴赫萨纳医院、埃尔朗根纽伦堡大学、汉堡大学、中国台湾大学、巴西圣保罗癌症研究所、美国NSABP研究基金会、佛罗里达大学、匹兹堡大学、阿勒格尼癌症研究所、普罗维登斯波特兰医疗中心、斯坦福大学、基因泰克、耶鲁大学、弗吉尼亚联邦大学、西班牙马德里大学、法国蒙彼利埃大学、墨西哥国家癌症研究所、爱尔兰肿瘤学研究协作组、意大利圣若望二十三世教皇医院、罗氏英国研发中心、罗氏中国、复旦大学附属肿瘤医院邵志敏等学者代表KATHERINE研究协作组起草的中期分析报告，比较了T-DM1或曲妥珠单抗二线辅助治疗HER2阳性早期乳腺癌患者的有效性和安全性。

KATHERINE: A Study of Trastuzumab Emtansine (Kadcyla) Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (NCT01772472)

　　该国际多中心3期随机非盲对照研究于2013年4月～2015年12月从28个国家地区273家医疗机构入组HER2阳性早期乳腺癌术前曲妥珠单抗＋紫杉类±蒽环类新辅助化疗后术中发现乳房或腋窝残留浸润病变患者1486例，按1∶1随机分为T-DM1组743例（每3周静脉注射3.6mg/kg）和曲妥珠单抗组743例（每3周静脉注射6mg/kg），术后辅助治疗3周×14次。主要研究终点为无浸润病变生存（定义为无同侧浸润性乳腺肿瘤复发、同侧局部区域浸润性乳腺癌复发、对侧浸润性乳腺癌、远处复发或任何原因所致死亡）。

　　根据中期分析结果，T-DM1组与曲妥珠单抗组相比：

• 中位随访时间：41.4、40.9个月

• 浸润病变或死亡率：12.2%、22.2%（91比165例）

• 无浸润病变生存率：88.3%、77.0%（风险比：0.50，95%置信区间：0.39～0.64，P<0.001）

• 首发浸润病变事件即为远处复发：10.5%、15.9%

• 不良事件发生率：98.8%比93.3%

• ≥3级不良事件发生率：25.7%比15.4%

• 严重不良事件发生率：12.7%比8.1%

• 不良事件所致死亡率：0.1%比0（1比0例）

　　因此，该研究结果表明，对于术前新辅助治疗完成后残留浸润病变的HER2阳性早期乳腺癌患者，T-DM1与曲妥珠单抗相比，术后二线辅助治疗的浸润性乳腺癌复发或死亡风险减少50%。

N Engl J Med. 2018 Dec 5. [Epub ahead of print]

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.

Gunter von Minckwitz, Chiun-Sheng Huang, Max S. Mano, Sibylle Loibl, Eleftherios P. Mamounas, Michael Untch, Norman Wolmark, Priya Rastogi, Andreas Schneeweiss, Andres Redondo, Hans H. Fischer, William Jacot, Alison K. Conlin, Claudia Arce-Salinas, Irene L. Wapnir, Christian Jackisch, Michael P. DiGiovanna, Peter A. Fasching, John P. Crown, Pia Wülfing, Zhimin Shao, Elena Rota Caremoli, Haiyan Wu, Lisa H. Lam, David Tesarowski, Melanie Smitt, Hannah Douthwaite, Stina M. Singel, Charles E. Geyer, Jr; KATHERINE Investigators.

German Breast Group, Neu-Isenburg; Center for Hematology and Oncology Bethanien, Frankfurt; AGO-B and HELIOS Klinikum Berlin-Buch, Berlin; National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg; Evangelische Kliniken Gelsenkirchen, Gelsenkirchen; Arbeitsgemeinschaft Gynakologische Onkologie - Breast and Sana Klinikum Offenbach, Offenbach; University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen; Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg, Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Instituto do Cancer do Estado de Sao Paulo, Sao Paulo; National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation and Orlando Health University of Florida Health Cancer Center, Orlando; NSABP Foundation and Allegheny Health Network Cancer Institute, NSABP Foundation and University of Pittsburgh Cancer Institute, School of Medicine, Pittsburgh; Hospital Universitario La Paz-Instituto de Investigación Hospital Universitario La Paz, Madrid; Institut Régional du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier, France; NSABP Foundation and Providence Portland Medical Center, Portland, OR; National Cancer Institute, Mexico City; NSABP Foundation and Stanford University School of Medicine, Stanford; Genentech, South San Francisco, California; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT; Ireland Cooperative Oncology Research Group, Dublin; Fudan University Shanghai Cancer Center; Roche (China) Holding, Shanghai; Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom; NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond.

BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.

METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).

RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.

CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone.

Funded by F. Hoffmann-La Roche/Genentech

KATHERINE ClinicalTrials.gov number: NCT01772472

DOI: 10.1056/NEJMoa1814017

以下广告内容与本微信公众号无关