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使用 sacituzumab govitecan 治疗转移性三阴性乳腺癌。

Tackling metastatic triple-negative breast cancer with sacituzumab govitecan.

机构信息

Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Department of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

出版信息

Expert Rev Anticancer Ther. 2021 Dec;21(12):1303-1311. doi: 10.1080/14737140.2021.1993065. Epub 2021 Oct 22.

Abstract

Metastatic triple-negative breast cancer (TNBC) is an aggressive cancer with poor survival that is difficult to treat due to a lack of targeted options. Conventional therapies targeting hormone receptors (HR) and human epidermal growth factor 2 (HER2) are ineffective and often chemotherapy is standard-of-care. Sacituzumab govitecan is an antibody drug conjugate (ADC) comprised of an active metabolite of irinotecan, SN-38, bound to a humanized monoclonal antibody targeting trophoblastic cell-surface antigen 2 (Trop-2). Trop-2 is highly expressed on the surface of TNBC cells, making it an attractive target. We explore the mechanism, pharmacology, efficacy, safety, and tolerability of sacituzumab govitecan. A literature search was conducted via PubMed using keywords such as 'sacituzumab govitecan,' and 'metastatic TNBC.' Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial. Common adverse effects were neutropenia, diarrhea, and nausea, however these effects were manageable with supportive care. Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers. It is likely we will see this therapy used in combination with other novel targeted agents as current clinical trials mature.

摘要

转移性三阴性乳腺癌(TNBC)是一种侵袭性癌症,生存预后较差,由于缺乏靶向选择,治疗难度大。针对激素受体(HR)和人表皮生长因子 2(HER2)的常规治疗无效,通常化疗是标准治疗。Sacituzumab govitecan 是一种抗体药物偶联物(ADC),由伊立替康的活性代谢物 SN-38 与针对滋养细胞表面抗原 2(Trop-2)的人源化单克隆抗体结合而成。Trop-2 在 TNBC 细胞表面高度表达,使其成为一个有吸引力的靶标。我们探讨了 sacituzumab govitecan 的作用机制、药理学、疗效、安全性和耐受性。通过 PubMed 进行文献检索,使用了“sacituzumab govitecan”和“转移性 TNBC”等关键词。基于 ASCENT 试验的数据,sacituzumab govitecan 为先前治疗过的 mTNBC 患者带来了有希望的生存获益。常见的不良反应是中性粒细胞减少、腹泻和恶心,但这些不良反应通过支持性护理是可以控制的。Sacituzumab govitecan 在除 TNBC 之外的癌症中也显示出了前景,如膀胱癌和肺癌,并且正在 HR 阳性乳腺癌中进行评估。随着当前临床试验的成熟,我们很可能会看到这种疗法与其他新型靶向药物联合使用。

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