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阿替利珠单抗治疗结直肠癌:最新证据和临床潜力。

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential.

机构信息

a Department of Medical Oncology , The Queen Elizabeth Hospital , Adelaide , South Australia , Australia.

b University of Adelaide , Adelaide , South Australia , Australia.

出版信息

Expert Opin Biol Ther. 2018 Apr;18(4):449-457. doi: 10.1080/14712598.2018.1444024. Epub 2018 Feb 23.

Abstract

Atezolizumab is a fully humanized, engineered monoclonal antibody that specifically targets PD-L1, key molecule in the cancer-immunity pathway. Atezolizumab is currently approved for the treatment of metastatic non-small-cell lung cancer and advanced urothelial carcinomas. Areas covered: In this review, we will present the available data supporting the efficacy of atezolizumab for the treatment of metastatic colorectal cancer (mCRC). We will also provide an update on the ongoing/future clinical trials evaluating the role of atezolizumab for the treatment of CRC in different settings (alone or in combination with other checkpoint inhibitors and/or targeted therapies). So far, a small subgroup of mCRC (those with deficiency in mismatch repair - dMMR) appears to benefit significantly from checkpoint inhibitors. As expected, further research is needed to develop biomarkers, effective therapeutic strategies and novel combinations to overcome immune escape resistance and achieve better responses with minimal toxicities. Expert opinion: Interim analyses from ongoing early-phase studies in mCRC have shown encouraging activity of atezolizumab in combination with chemotherapy and/or targeted therapies, especially with MEK inhibitor cobimetinib. Within the next few years, this PD-L1 checkpoint inhibitor will likely be included as one of the treatment options for CRC, at least for patients with dMMR.

摘要

阿替利珠单抗是一种完全人源化、工程化的单克隆抗体,特异性靶向 PD-L1,这是癌症免疫途径中的关键分子。阿替利珠单抗目前被批准用于治疗转移性非小细胞肺癌和晚期尿路上皮癌。

涵盖领域

在这篇综述中,我们将介绍支持阿替利珠单抗治疗转移性结直肠癌(mCRC)疗效的现有数据。我们还将提供正在进行/未来评估阿替利珠单抗在不同情况下(单独或与其他检查点抑制剂和/或靶向治疗联合)治疗 CRC 作用的临床试验的最新情况。到目前为止,一小部分 mCRC(那些存在错配修复缺陷 - dMMR)似乎明显受益于检查点抑制剂。正如预期的那样,需要进一步的研究来开发生物标志物、有效的治疗策略和新的组合,以克服免疫逃逸耐药性,并实现更好的反应,同时最小化毒性。

专家意见

正在进行的 mCRC 早期研究的中期分析显示,阿替利珠单抗联合化疗和/或靶向治疗具有令人鼓舞的活性,尤其是与 MEK 抑制剂 cobimetinib 联合使用时。在未来几年内,这种 PD-L1 检查点抑制剂很可能被纳入 CRC 的治疗选择之一,至少对于 dMMR 患者是如此。

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