恩美曲妥珠能否取代曲妥珠＋紫杉醇

　　对于HER2阳性早期乳腺癌，曲妥珠单抗＋紫杉醇化疗是术后辅助治疗标准方案之一。恩美曲妥珠单抗（T-DM1）将毒性更强的化疗药物DM1缀合于曲妥珠单抗，直击肿瘤灵魂深处，可有效提高抗肿瘤疗效和安全性。那么，恩美曲妥珠单抗能否取代曲妥珠单抗＋紫杉醇化疗？

　　2021年6月2日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表哈佛大学医学院、达纳法伯癌症研究所、麻省总医院、贝斯以色列医院和新英格兰女执事医院、纽约纪念医院斯隆凯特林癌症中心、萨拉坎农研究所、田纳西肿瘤医院、范德4大学英格拉姆癌症中心、德克萨斯大学MD安德森癌症中心、贝勒医学院丹邓肯综合癌症中心、圣路易斯华盛顿大学、霍普金斯大学西德尼金梅尔癌症中心、乔治城大学医学中心、伦巴第综合癌症中心、北卡罗来纳大学、旧金山加利福尼亚大学、俄勒冈州立大学综合癌症中心、爱达荷州立圣卢克山州肿瘤研究所、维克森林大学浸会医院、西雅图华盛顿大学、芝加哥伊利诺伊大学、芝加哥大学、长岛犹太医疗中心癌症研究所、印第安纳大学医学院、北光癌症中心、杜克大学、洛约拉大学医学中心、哈特福德医院癌症研究所、洛厄尔综合医院、宾夕法尼亚大学阿伯拉姆森癌症中心、密歇根大学罗杰尔癌症中心、伯明翰阿拉巴马大学柯克林肿瘤医院、梅奥医学中心的ATEMPT研究报告，比较了恩美曲妥珠单抗与曲妥珠单抗＋紫杉醇辅助化疗对HER2阳性早期乳腺癌术后患者的有效性和安全性。

ATEMPT (NCT01853748): A Randomized Phase II Study of Trastuzumab Emtansine (T-DM1) vs. Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer

　　该多中心非盲随机对照二期临床研究于2013年5月17日～2016年12月13日从24家医院入组集中确诊的HER2阳性一期乳腺癌术后患者497例，按3∶1随机分为两组：

  • 恩美曲妥珠单抗组383例：每3周静脉注射恩美曲妥珠单抗3.6mg/kg×51周

  • 紫杉曲妥珠单抗组114例：每周静脉注射紫杉醇80mg/m²＋曲妥珠单抗首次4mg/kg随后2mg/kg×12周，随后每3周静脉注射曲妥珠单抗6mg/kg×39周

　　两组共同主要目标为临床相关毒性发生率，恩美曲妥珠单抗组主要目标为无浸润癌生存率。

　　结果，恩美曲妥珠单抗组与紫杉曲妥珠单抗组相比：

  • 临床相关毒性发生率：46%比47%（P=0.83）

  • 三年无浸润癌生存率：97.8%（95%置信区间：96.3～99.3，P<0.0001）

　　连续收集患者报告结局表明，恩美曲妥珠单抗组与紫杉曲妥珠单抗组相比，神经病变、脱发发生率较低，工作效率较高。

　　因此，该二期临床研究结果表明，对于一期HER2阳性乳腺癌术后患者，1年恩美曲妥珠单抗辅助治疗的3年无浸润癌生存率较高，与紫杉醇＋曲妥珠单抗相比，临床相关毒性发生率相似，神经病变、脱发发生率较低，工作效率较高。

J Clin Oncol. 2021 Jun 2. Online ahead of print.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial.

Sara M. Tolaney, Nabihah Tayob, Chau Dang, Denise A. Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Jiani Hu, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope S. Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Frederick Briccetti, Bryan Schneider, Audrey Merrill Garrett, Kelly Marcom, Kathy Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta Liu, Kathryn Ruddy, Yue Zheng, Shoshana M. Rosenberg, Richard D. Gelber, Lorenzo Trippa, William Barry, Michelle DeMeo, Harold Burstein, Ann Partridge, Eric P. Winer, Ian Krop.

Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Massachusetts General Hospital, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA; Memorial Sloan Kettering Cancer Center, New York, NY; Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Vanderbilt-Ingram Cancer Center, Nashville, TN; The University of Texas MD Anderson Cancer Center, Houston, TX; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX; Washington University, St Louis, MO; Johns Hopkins Sidney Kimmel Cancer Center, Washington, DC; Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC; UNC Chapel Hill, Chapel Hill, NC; UCSF, San Francisco, CA; OSU Comprehensive Cancer Center, Columbus, OH; St Luke's Mountain States Tumor Institute, Boise, ID; Wake Forest Baptist Health, Winston-Salem, NC; University of Washington, Seattle, WA; University of Illinois at Chicago, Chicago, IL; The University of Chicago, Chicago, IL; North Shore-LIJ Cancer Institute, Lake Success, NY; IU School of Medicine, Indianapolis, IN; Northern Light Cancer Care, Brewer, ME; Duke University, Durham, NC; Loyola University Medical Center, Maywood, IL; Hartford Healthcare Cancer Institute, Hartford, CT; Lowell General Hospital, Lowell, MA; Abramsom Cancer Center, University of Pennsylvania, Philadelphia, PA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI; Kirklin UAB Hematology Oncology, Birmingham, AL; Mayo Clinic, Rochester, MN.

PURPOSE: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

METHODS: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1.

RESULTS: The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH (P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis (P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH.

CONCLUSION: Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH.

KEY OBJECTIVE: Does trastuzumab emtansine (T-DM1) cause less toxicity than paclitaxel plus trastuzumab (TH) and is T-DM1 associated with a clinically acceptable invasive disease-free survival among patients with stage I human epidermal growth factor receptor 2-positive breast cancer?

KNOWLEDGE GENERATED: The 3-year invasive disease-free survival for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), but there was no difference in the rate of clinically relevant toxicities between arms (46% v 47%, P = .83).

RELEVANCE: T-DM1 may be considered as an alternative treatment to TH for selected patients with stage I human epidermal growth factor receptor 2-positive disease.

PMID: 34077270

DOI: 10.1200/JCO.20.03398

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