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Development and validation of a prognostic model for patients with advanced lung cancer treated with the immune checkpoint inhibitor atezolizumab.

免疫检查点抑制剂 atezolizumab 治疗晚期肺癌患者预后模型的开发和验证。

  • 影响因子:8.32
  • DOI:10.1158/1078-0432.CCR-19-2968
  • 作者列表:"Hopkins AM","Kichenadasse G","Garrett-Mayer E","Karapetis CS","Rowland A","Sorich MJ
  • 发表时间:2020-02-21
Abstract

PURPOSE:Immune checkpoint inhibitors (ICI) are a significant advance to the treatment of advanced non-small cell lung cancer (NSCLC), however, their initiation is associated with heterogeneity in outcomes. This study aimed to develop and validate a prognostic tool of survival in advanced NSCLC patients treated with ICIs. EXPERIMENTAL DESIGN:A pre-treatment prognostic model was developed and validated using clinicopathological data. Development data consisted of advanced NSCLC patients treated with atezolizumab from the randomised trials OAK and POPLAR (n=751). Data from the single-arm atezolizumab trials BIRCH and FIR (n=797) were used for external validation. Prognostic scores were categorised into low, intermediate-low, intermediate, intermediate-high and high-risk prognostic groups. The primary outcome was overall survival (OS), with progression-free survival (PFS) secondary. RESULTS:Pre-treatment C-reactive protein (CRP) was the most predictive variable for OS. The prognostic tool was optimally defined by CRP, lactate dehydrogenase, derived neutrophil-to-lymphocyte ratio, albumin, PD-L1 expression, performance status, time since metastatic diagnosis, and metastatic sites count. Prognostic groups had significantly different OS (c-statistic=0.72), with median OS ranging from >24 to 3 months for the low to high-risk groups. Performance was maintained on validation (c=0.76). Findings were similar for PFS, with median PFS ranging from 5 to 1 month for the low to high-risk groups. Benefit of atezolizumab (versus docetaxel) was greatest in the low-risk group (>3 months median OS improvement), with little benefit apparent for the highest-risk group. CONCLUSIONS:A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.

摘要

目的: 免疫检查点抑制剂 (ICI) 是晚期非小细胞肺癌 (NSCLC) 治疗的一个重大进展,然而,它们的启动与结局的异质性相关。本研究旨在开发和验证接受 ICIs 治疗的晚期 NSCLC 患者的生存预后工具。 实验设计: 开发了治疗前预后模型,并使用临床病理数据进行了验证。发展数据包括来自随机试验 OAK 和 pomber (n = 751) 的接受 atezolizumab 治疗的晚期 NSCLC 患者。来自单组 atezolizumab 试验 (BIRCH 和 FIR,n = 797) 的数据用于外部验证。预后评分分为低、中-低、中、中高和高危预后组。主要结局为总生存期 (OS),无进展生存期 (PFS) 为次要。 结果: 治疗前 C 反应蛋白 (CRP) 是 OS 的最预测变量。通过 CRP 、乳酸脱氢酶、中性粒细胞与淋巴细胞比值、白蛋白、 PD-L1 表达、性能状态、转移诊断时间和转移部位计数来确定预后工具。预后组有显著不同的 OS (c-statistics = 0.72),低至高风险组的中位 OS 范围为> 24 至 3 个月。验证时保持性能 (c = 0.76)。PFS 的结果相似,低至高危组的中位 PFS 为 5 ~ 1 个月。在低风险组中,atezolizumab (与多西他赛相比) 的获益最大 (> 3 个月中位 OS 改善),而在高风险组中几乎没有明显的获益。 结论: 开发并验证了一个预后工具,以确定在晚期 NSCLC 开始使用 atezolizumab 后具有明显不同生存期的患者组。

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