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Tucatinib+曲妥珠单抗+卡培他滨治疗HER2阳性转移性乳腺癌延长生存期
作者:小柯机器人 发布时间:2019/12/17 16:37:53

美国达纳法伯癌症研究所Eric P. Winer联合德克萨斯大学安德森肿瘤中心Rashmi K. Murthy团队的一项最新研究,探讨了Tucatinib+曲妥珠单抗+卡培他滨治疗HER2阳性转移性乳腺癌的疗效。2019年12月11日,国际知名学术期刊《新英格兰医学杂志》发表了这一成果。

人表皮生长因子受体2(HER2)阳性转移性的乳腺癌患者经多个HER2靶向药物治疗后病情进展,其选择极其有限。Tucatinib是一种研究性、口服、高选择性的HER2酪氨酸激酶抑制剂。

研究组招募了480名HER2阳性的转移性乳腺癌患者,此前他们均接受过曲妥珠单抗、帕妥珠单抗和曲妥珠单抗-美坦新治疗,伴或不伴脑转移。将其随机分组,分别接受Tucatinib或安慰剂联合曲妥珠单抗+卡培他滨进行治疗。

Tucatinib联合组和安慰剂联合组治疗1年的无进展生存率分别为33.1%和12.3%,差异显著,中位无进展生存期分别为7.8个月和5.6个月。Tucatinib联合组和安慰剂联合组治疗2年的总生存率分别为44.9%和26.6%,差异显著,中位总生存期分别为21.9个月和17.4个月。

在脑转移患者中,Tucatinib联合组1年无进展生存率为24.9%,安慰剂联合组为0%,差异显著,中位无进展生存期分别为7.6个月和5.4个月。Tucatinib组常见的不良反应包括腹泻、掌跖感觉障碍综合征、恶心、疲劳和呕吐。Tucatinib联合组中3级及以上腹泻和转氨酶升高的发生率显著高于安慰剂联合组。

总之,在HER2阳性转移性乳腺癌包括脑转移的重度患者中,与安慰剂相比,曲妥珠单抗+卡培他滨+Tucatinib显著提高了无进展生存率和总生存率,但亦增加了腹泻和转氨酶升高的风险。

附:英文原文

Title: Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer

Author: Rashmi K. Murthy, M.D.,, Sherene Loi, M.D.,, Alicia Okines, M.D.,, Elisavet Paplomata, M.D.,, Erika Hamilton, M.D.,, Sara A. Hurvitz, M.D.,, Nancy U. Lin, M.D.,, Virginia Borges, M.D.,, Vandana Abramson, M.D.,, Carey Anders, M.D.,, Philippe L. Bedard, M.D.,, Mafalda Oliveira, M.D.,, Erik Jakobsen, M.D.,, Thomas Bachelot, M.D.,, Shlomit S. Shachar, M.D.,, Volkmar Müller, M.D.,, Sofia Braga, M.D.,, Francois P. Duhoux, M.D.,, Richard Greil, M.D.,, David Cameron, M.D.,, Lisa A. Carey, M.D.,, Giuseppe Curigliano, M.D., Ph.D.,, Karen Gelmon, M.D.,, Gabriel Hortobagyi, M.D.,, Ian Krop, M.D., Ph.D.,, Sibylle Loibl, M.D.,, Mark Pegram, M.D.,, Dennis Slamon, M.D.,, M. Corinna Palanca-Wessels, M.D., Ph.D.,, Luke Walker, M.D.,, Wentao Feng, Ph.D.,, and Eric P. Winer, M.D.

Issue&Volume: December 11, 2019

Abstract: 

Background
 
Patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer who have disease progression after therapy with multiple HER2-targeted agents have limited treatment options. Tucatinib is an investigational, oral, highly selective inhibitor of the HER2 tyrosine kinase.
 
Methods
 
We randomly assigned patients with HER2-positive metastatic breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine, who had or did not have brain metastases, to receive either tucatinib or placebo, in combination with trastuzumab and capecitabine. The primary end point was progression-free survival among the first 480 patients who underwent randomization. Secondary end points, assessed in the total population (612 patients), included overall survival, progression-free survival among patients with brain metastases, confirmed objective response rate, and safety.
 
Results
 
Progression-free survival at 1 year was 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group (hazard ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.42 to 0.71; P<0.001), and the median duration of progression-free survival was 7.8 months and 5.6 months, respectively. Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P=0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar–plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.
 
Conclusions
 
In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo; the risks of diarrhea and elevated aminotransferase levels were higher with tucatinib. 
 
DOI: 10.1056/NEJMoa1914609

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1914609

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home