转移泌尿道癌控制点抑制剂的现代治疗能力

Р. А. Гафанов, Светлана Гармаш, И. Б. Кравцов, С. В. Фастовец
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引用次数: 0

摘要

长期以来,化疗一直是转移性尿路上皮癌(mUC)的主要治疗选择。在过去的一年中,随着五种新药的批准,发生了革命性的变化,这些新药旨在阻断t淋巴细胞表面蛋白PD-1与其配体PD-L1和PD-L2之间的相互作用,从而激活免疫反应。值得注意的是,在一项随机III期临床试验中,抗pd -1抗体派姆单抗(pembrolizumab)在二线mUC患者中显示出相对于化疗的总生存期增加。基于这一1级证据,派姆单抗获得了美国食品和药物管理局(FDA)的批准。与历史对照组相比,Nivolumab(抗体PD-1)也显示出总生存期的增加,并获得了FDA的批准。同样,靶向PD-L1的抗体,包括atezolizumab、durvalumab和avelumab,作为mUC的二线治疗获得了FDA的加速批准。根据II期研究的结果,其中一些药物在一线获得批准(atezolizumab和pembolizumab获得加速批准,可用于未接受顺铂的患者的一线治疗)。尽管有这么多的支持,临床开发新的生物标志物,以选择患者,谁可以获得免疫治疗的最大优势,并制定最佳的治疗序列,仍然是未来研究的最大和关键问题。临床引入生物标志物来确定患者的最佳治疗仍然非常重要。
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СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ ТЕРАПИИ ИНГИБИТОРАМИ КОНТРОЛЬНЫХ ТОЧЕК ПРИ МЕТАСТАТИЧЕСКОМ УРОТЕЛИАЛЬНОМ РАКЕ
For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC). Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T-lymphocytes PD-1 and its ligands PD-L1 and PD-L2, resulting in the activation of the immune response. It is noteworthy that the anti-PD-1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA). Nivolumab (antibody PD-1) also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD-L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first-line treatment in patients not receiving cisplatin). Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation. The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.
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