Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study
Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study
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ORIENT-11 3 期研究中信迪利单抗联合培美曲塞和铂作为局部晚期或转移性非鳞状 NSCLC 一线治疗的最新总体生存数据和预测生物标志物
DOI：
10.1016/j.jtho.2021.07.015
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发表时间：
2021-11-19
影响因子：
20.4
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Yang, Yunpeng;Sun, Jiya;Zhang, Li
简介：在ORIENT-11研究中，与单纯化疗相比，Sintiliumab联合化疗显著延长了非鳞状NSCLC的无进展生存期（PFS）。此处报告了更新的总生存期（OS）和PFS数据以及相应的生物标志物分析。研究方法：在这项研究中，共有397例既往未接受过治疗的局部晚期或转移性非鳞状NSCLC患者被分配到sintiliumab+化疗联合治疗（combo）组或安慰剂+化疗治疗组。根据程序性死亡配体1（PD-L1）表达水平对患者进行分层。肿瘤RNA测序和PD-L1免疫组织化学的免疫特征谱与临床结果相关，以识别预测性生物标志物。结果如下：截至2021年1月，中位随访时间为22.9个月，与安慰剂+化疗治疗组相比，联合治疗组的中位OS显著改善（未达到vs 16.8个月;风险比[HR] = 0.60，95%置信区间[CI]：0.45-0.79，p = 0.0003）。与不存在或低免疫细胞浸润相比，联合治疗组中高或中等免疫细胞浸润与PFS改善密切相关，这表明化疗不能引发“免疫沙漠”以从程序性细胞死亡蛋白-1抑制中获益。特别是，在联合治疗组中，高主要组织相容性复合体（MHC）II类呈递途径表达与PFS（HR = 0.32，95% CI：0.19-0.54，p < 0.0001）和OS（HR = 0.36，95% CI：0.20-0.64，p = 0.0005）延长显著相关。重要的是，PD L1低表达或缺失但MHC II类高表达的患者仍可从联合治疗中获益。相比之下，MHC I类抗原呈递途径在该组合设置中不太相关。结论：在非鳞状NSCLC患者中，在化疗基础上加用辛替利单抗可显著延长OS。MHCII类抗原呈递途径的表达可以识别从这种组合中获益最多的患者。(c)2021年国际肺癌研究协会。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Introduction: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. Methods: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. Results: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. Conclusions: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).