a National Centre for Asbestos Related Diseases , University of Western Australia , Crawley , Australia.
b Institute for Respiratory Health, University of Western Australia , Nedlands , Australia.
Expert Opin Biol Ther. 2019 Jul;19(7):697-706. doi: 10.1080/14712598.2019.1606209. Epub 2019 May 2.
Combination chemotherapy is currently standard care for advanced mesothelioma. Checkpoint blockade is a promising new treatment.
This review covers clinical use and biomarkers of checkpoint blockade. Medline search used keywords 'mesothelioma' combined with 'checkpoint blockade' OR 'PD-L1' OR 'PD1' OR 'anti-CTLA4'; the search terms AND 'clinical trial' or AND 'biomarker*' were added. Handsearching covered abstracts from relevant meetings from 2016 to 2018 and reference lists. Data informed a narrative review.
Single agent anti-CTLA4 blockade is inactive in mesothelioma. Single agent PD-1 blockade as second or subsequent treatment gives 20-29% partial responses; no randomized comparisons against placebo or chemotherapy are available. Biomarkers of response have been difficult to identify. There is no consensus as to whether tumor PD-L1 expression predicts outcomes. Combination checkpoint inhibitors (CTLA4 and PD1 blockade) provide a small incremental increase in response rates and progression-free survival. Chemoimmunotherapy is the next frontier.
联合化疗目前是治疗晚期间皮瘤的标准方法。检查点阻断是一种很有前途的新治疗方法。
本文综述了检查点阻断的临床应用和生物标志物。使用关键词“间皮瘤”结合“检查点阻断”或“PD-L1”或“PD1”或“抗 CTLA4”在 Medline 上进行搜索；并添加了“临床试验”或“生物标志物*”的搜索词。手工搜索涵盖了 2016 年至 2018 年相关会议的摘要和参考文献列表。数据为叙述性综述提供了信息。
单一的抗 CTLA4 阻断在间皮瘤中无效。作为二线或后续治疗的单一 PD-1 阻断治疗有 20-29%的部分缓解率；没有针对安慰剂或化疗的随机比较。反应的生物标志物一直难以确定。肿瘤 PD-L1 表达是否预测预后尚无共识。联合检查点抑制剂（CTLA4 和 PD1 阻断）可略微提高反应率和无进展生存期。化疗免疫治疗是下一个前沿。
