College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Department of Medical Oncology, Flinders Medical Centre, Adelaide, Australia.
Clin Cancer Res. 2020 Jul 1;26(13):3280-3286. doi: 10.1158/1078-0432.CCR-19-2968. Epub 2020 Feb 21.
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 patients with advanced NSCLC treated with ICIs.
A pretreatment prognostic model was developed and validated using clinicopathologic data. Development data consisted of patients with advanced NSCLC treated with atezolizumab from the randomised trials OAK and POPLAR ( = 751). Data from the single-arm atezolizumab trials BIRCH and FIR ( = 797) were used for external validation. Prognostic scores were categorized 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.
Pretreatment 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 site count. Prognostic groups had significantly different OS (-statistic = 0.72), with median OS ranging from >24 to 3 months for the low- to high-risk groups. Performance was maintained on validation ( = 0.76). These findings were similar for PFS, with median PFS ranging from 5 months to 1 month for the low- to high-risk groups. Benefit of atezolizumab (vs. docetaxel) was greatest in the low-risk group (>3 months median OS improvement), with little benefit apparent for the highest risk group.
A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.
免疫检查点抑制剂（ICI）是治疗晚期非小细胞肺癌（NSCLC）的重大进展；然而，其起始与结局的异质性相关。本研究旨在开发和验证接受ICI 治疗的晚期 NSCLC 患者生存的预后工具。
使用临床病理数据开发和验证了一种预处理预后模型。开发数据包括接受阿特珠单抗治疗的晚期 NSCLC 患者，这些患者来自随机试验 OAK 和 POPLAR（n=751）。来自单臂阿特珠单抗试验 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。主要结局是总生存期（OS），次要结局是无进展生存期（PFS）。
治疗前 C 反应蛋白（CRP）是 OS 最具预测性的变量。该预后工具通过 CRP、乳酸脱氢酶、衍生中性粒细胞与淋巴细胞比值、白蛋白、PD-L1 表达、体能状态、转移性诊断后时间和转移性部位计数进行最佳定义。预后组的 OS 差异具有统计学意义（-统计量=0.72），低危组至高危组的中位 OS 范围从>24 个月至 3 个月不等。验证时保持了性能（=0.76）。这些发现与 PFS 相似，低危组至高危组的中位 PFS 范围从 5 个月至 1 个月不等。与多西他赛相比，阿特珠单抗的获益最大（高危组 OS 改善超过 3 个月），对于最高危组获益不明显。
开发并验证了一种预后工具，用于识别接受阿特珠单抗治疗的晚期 NSCLC 患者中具有明显不同生存的患者群体。
