Boukouris Aristeidis E, Theochari Maria, Stefanou Dimitra, Papalambros Alexandros, Felekouras Evangelos, Gogas Helen, Ziogas Dimitrios C
First Department of Internal Medicine, Korgialeneion-Benakeion General Hospital, Athens, Greece.
First Department of Medicine, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Crit Rev Oncol Hematol. 2022 May;173:103663. doi: 10.1016/j.critrevonc.2022.103663. Epub 2022 Mar 26.
The long-term remissions induced by immune-checkpoint inhibitors (ICIs) in many types of cancers have opened up the possibility of a broader use of immunotherapy in less immunogenic but genetically heterogeneous tumours. Regarding metastatic colorectal cancer (mCRC), in first-line setting, pembrolizumab has been approved as preferred option and nivolumab, alone or in combination with ipilimumab as alternative option for patients with mismatch-repair-deficient and microsatellite instability-high (dMMR/MSI-H) disease, independently of their eligibility for intensive chemotherapy. In subsequent lines, both these immunotherapeutic regimens (e.g., pembrolizumab and nivolumab+/-ipilimumab) as well as dostarlimab-gxly are currently recommended for patients with dMMR/MSI-H chemo-resistant mCRC who have not previously received an ICI. Beginning from the rationale behind the immune-mediated interplay in the dMMR/MSI-H bowel microenvironment, we provide here an update on the evolution status of all available, approved or not, ICIs in mCRC, describing their efficacy and toxicity profile with an emphasis on the pivotal trials supporting current colorectal indications. For each ICI agent, the results from combinations under investigation, particularly for those being upgraded in clinical phasing, the perspectives but also the limitations of main ongoing trials are thoroughly discussed. In the close future, upcoming data are expected to confirm the clinical benefit of ICIs and to further expand their role in mCRC.
免疫检查点抑制剂（ICI）在多种癌症中诱导的长期缓解，为在免疫原性较低但基因异质性的肿瘤中更广泛地使用免疫疗法开辟了可能性。对于转移性结直肠癌（mCRC），在一线治疗中，帕博利珠单抗已被批准为首选，纳武利尤单抗单独或与伊匹木单抗联合作为错配修复缺陷和微卫星高度不稳定（dMMR/MSI-H）疾病患者的替代选择，无论其是否适合强化化疗。在后续治疗线中，目前推荐这两种免疫治疗方案（如帕博利珠单抗和纳武利尤单抗±伊匹木单抗）以及多斯塔利单抗-gxly用于既往未接受过ICI的dMMR/MSI-H化疗耐药mCRC患者。从dMMR/MSI-H肠道微环境中免疫介导相互作用的基本原理出发，我们在此提供mCRC中所有可用的、已批准或未批准的ICI的进展情况更新，描述它们的疗效和毒性特征，重点介绍支持当前结直肠癌适应证的关键试验。对于每种ICI药物，深入讨论了正在研究的联合用药结果，特别是那些正在进入临床阶段升级的联合用药，以及主要正在进行试验的前景和局限性。在不久的将来，预计即将获得的数据将证实ICI的临床益处，并进一步扩大它们在mCRC中的作用。
