Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
Multicentre biomarker cohort study on the efficacy of nivolumab treatment for gastric cancer
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DOI：
10.1038/s41416-020-0975-7
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发表时间：
2020-07-03
影响因子：
8.8
通讯作者：
Doki, Yuichiro
中科院分区：
文献类型：
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作者：
Hagi, Takaomi;Kurokawa, Yukinori;Doki, Yuichiro
背景：胃癌（GC）患者纳武单抗治疗反应的预测因素尚不清楚。方法在这项回顾性队列研究中，收集了2017年9月至2019年2月期间来自23家机构的不可切除或复发性胃癌患者的组织标本，这些患者先前或计划接受纳武单抗作为三线或更高治疗。免疫组化分析PD-L1表达和错配修复（MMR）的肿瘤阳性评分（TPS）和联合阳性评分（CPS）。评估临床病理因素与肿瘤反应率、超进展性疾病（HPD）率和生存率之间的关系。结果在200例符合条件的患者中，143例有可测量的病变。有效率为17.5%，HPD率为22.1%。表现状态（PS） 0-1 （P = 0.026）、非腹膜转移（P = 0.021）、PD-L1 TPS >= 1 （P = 0.012）、CPS >= 5 （P = 0.007）或>= 10 （P < 0.001）或MMR缺乏（P < 0.001）患者的有效率显著较高。ps2 -3 （P = 0.026）、肝转移（P < 0.001）、CPS < 10 （P = 0.048）患者的HPD率显著高于其他患者。多因素分析显示，CPS （P = 0.001）、MMR （P = 0.002）、肝转移（P < 0.001）、腹膜转移（P = 0.004）、CRP （P < 0.001）是影响无进展生存期的独立预后因素。结论PD-L1 CPS和MMR可作为纳武单抗治疗GC疗效的有效生物标志物。
Background Predictive factors of nivolumab treatment response in patients with gastric cancer (GC) remain unclear. Methods In this retrospective cohort study, tissue specimens of patients with unresectable or recurrent GC and prior or scheduled treatment with nivolumab as third-line or higher therapy between September 2017 and February 2019 were collected from 23 institutions. The tumour-positive score (TPS) and combined positive score (CPS) of PD-L1 expression and mismatch repair (MMR) were analysed by immunohistochemistry. Associations between clinicopathological factors and tumour-response rate, hyperprogressive disease (HPD) rate and survival were assessed. Results Of 200 eligible patients, 143 had measurable lesions. The response and HPD rates were 17.5% and 22.1%, respectively. The response rate was significantly higher in patients with performance status (PS) 0-1 (P = 0.026), non-peritoneal metastasis (P = 0.021), PD-L1 TPS >= 1 (P = 0.012), CPS >= 5 (P = 0.007) or >= 10 (P < 0.001) or MMR deficiency (P < 0.001). The HPD rate was significantly higher in patients with PS 2-3 (P = 0.026), liver metastasis (P < 0.001) and CPS < 10 (P = 0.048). Multivariate analysis revealed that CPS (P = 0.001) and MMR (P = 0.002) were independent prognostic factors of progression-free survival, as well as liver metastasis (P < 0.001), peritoneal metastasis (P = 0.004) and CRP (P < 0.001). Conclusions PD-L1 CPS and MMR could be useful biomarkers for nivolumab treatment efficacy in GC.