一种新的血细胞计数评分，用于预测接受阿特珠单抗治疗的非小细胞肺癌患者的早期生存：四项多中心临床试验的综合分析。
Definition of a new blood cell count score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of four multicenter clinical trials.
机构信息
Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Department of Radiation Oncology, Translational Radiobiology, Universitätsklinikum Erlangen, Erlangen, Germany.
出版信息
Front Immunol. 2022 Sep 2;13:961926. doi: 10.3389/fimmu.2022.961926. eCollection 2022.
IMPORTANCE
Blood cell count test (BCT) is a robust method that provides direct quantification of various types of immune cells to reveal the immune landscape to predict atezolizumab treatment outcomes for clinicians to decide the next phase of treatment.
OBJECTIVE
This study aims to define a new BCTscore model to predict atezolizumab treatment benefits in non-small lung cell cancer (NSCLC) patients.
DESIGN SETTING AND PARTICIPANTS
This study analyzed four international, multicenter clinical trials (OAK, BIRCH, POPLAR, and FIR trials) to conduct analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment ( = 1,479) or docetaxel single-agent treatment ( = 707). BCT was conducted at three time points: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients.
MAIN OUTCOMES AND MEASURES
Overall survival (OS) was used as the primary end point, whereas progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST), clinical benefit (CB), and objective response rate (ORR) were used as secondary end points.
RESULTS
The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at time point T3 and neutrophil-to-monocyte ratio (NMR) at time point T2 with absolute cutoff values of NLR_T3 = 5, PLR_T3 = 180, and NMR_T2 = 6 were identified as strong predictive biomarkers for atezolizumab (Ate)-treated NSCLC patients in comparison with docetaxel (Dtx)-treated patients regarding OS (BCTscore low risk: HR vs = 1.54 (95% CI: 1.04-2.27), = 0.031; high risk: HR vs = 0.84 (95% CI: 0.62-1.12), = 0.235). The identified BCTscore model showed better OS AUC in the OAK (AUC = 0.696), BIRCH (AUC = 0.672) and POPLAR+FIR studies (AUC = 0.727) than that of each of the three single BCT biomarkers.
CONCLUSION AND RELEVANCE
The BCTscore model is a valid predictive and prognostic biomarker for early survival prediction in atezolizumab-treated NSCLC patients.
重要性
血细胞计数测试（BCT）是一种强大的方法，可直接定量各种类型的免疫细胞，以揭示免疫景观，从而预测阿特珠单抗治疗结果，为临床医生提供决策下一阶段治疗的依据。
目的
本研究旨在定义一种新的 BCTscore 模型，以预测非小细胞肺癌（NSCLC）患者接受阿特珠单抗（抗 PD-L1）单药治疗的获益。
设计、设置和参与者：本研究分析了四项国际多中心临床试验（OAK、BIRCH、POPLAR 和 FIR 试验），对接受阿特珠单抗（anti-PD-L1）单药治疗（n = 1479）或多西他赛单药治疗（n = 707）的 NSCLC 患者进行了分析。BCT 在三个时间点进行：治疗前（T1）、治疗第 3 周期第 1 天（T2）和治疗第 5 周期第 1 天（T3）。进行单变量和多变量 Cox 回归分析，以确定早期 BCT 生物标志物，预测 NSCLC 患者接受阿特珠单抗治疗的结果。
主要结果和测量指标
总生存期（OS）作为主要终点，而根据实体瘤反应评价标准（RECIST）的无进展生存期（PFS）、临床获益（CB）和客观缓解率（ORR）作为次要终点。
结果
T3 时间点的中性粒细胞与淋巴细胞比值（NLR）和血小板与淋巴细胞比值（PLR）以及 T2 时间点的中性粒细胞与单核细胞比值（NMR）的 BCT 生物标志物，其绝对截断值为 NLR_T3 = 5、PLR_T3 = 180 和 NMR_T2 = 6，与多西他赛（Dtx）治疗患者相比，这些标志物被确定为接受阿特珠单抗（Ate）治疗的 NSCLC 患者的强有力的预测生物标志物，与 OS 相关（BCTscore 低危风险：HR vs = 1.54（95%CI：1.04-2.27）， = 0.031；高危风险：HR vs = 0.84（95%CI：0.62-1.12）， = 0.235）。与三个单一 BCT 生物标志物中的每一个相比，所确定的 BCTscore 模型在 OAK（AUC = 0.696）、BIRCH（AUC = 0.672）和 POPLAR+FIR 研究（AUC = 0.727）中显示出更好的 OS AUC。
结论和相关性
BCTscore 模型是一种有效的预测和预后生物标志物，可用于预测接受阿特珠单抗治疗的 NSCLC 患者的早期生存。
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