Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-11-09 DOI:10.1016/j.lungcan.2024.108017

Hiroaki Akamatsu , Yasuhiro Koh , Makoto Nishio , Yasushi Goto , Hidetoshi Hayashi , Satoru Miura , Koji Tamada , Hiroshi Kagamu , Akihiko Gemma , Ichiro Yoshino , Toshihiro Misumi , Atsuto Mouri , Ryota Saito , Naoto Takase , Noriko Yanagitani , Hiroshi Nokihara , Masahiro Seike , Kei Takamura , Masahide Mori , Shunichiro Iwasawa , Tetsuya Mitsudomi

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引用次数: 0

Abstract

Objectives

Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting.

Materials and Methods

This was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab.

Results

Among the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low.

Conclusion

Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.

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血清生物标记物综合分析显示，IL-8的变化是晚期非小细胞肺癌患者使用免疫检查点抑制剂疗效的唯一预测指标。

目的：程序性细胞死亡配体 1（PD-L1）的表达被广泛用于预测 PD-(L)1 抑制剂的有效性，尽管它并不完美。以往的研究建议使用各种血清生物标记物；然而，由于样本量有限或许多研究只关注单一生物标记物，研究结果并不确定。本研究对多重血清生物标志物进行了分析，以探索它们在现实世界中对接受PD-L1抑制剂治疗的大样本晚期非小细胞肺癌（NSCLC）患者的预测能力：这是J-TAIL的一项子研究，J-TAIL是一项针对晚期NSCLC预处理患者的阿特珠单抗单药治疗的前瞻性观察研究。2019年4月至10月，日本73个研究机构共招募了262名患者。在基线和第二次服用阿特珠单抗时采集血清样本。使用 Luminex 平台对 51 种血清细胞因子、趋化因子、生长因子和血管内皮生长因子进行定量。研究了基线值以及第二次用药时间与基线值的折叠变化与阿特珠单抗疗效的关系：在评估的51种蛋白质中，较高的白细胞介素（IL）-12基线水平、较高的可溶性CD40配体折叠变化、较低的IL-8折叠变化与较高的客观应答率（ORR）相关。其中，只有较低的IL-8折叠变化与较好的无进展生存期（PFS）相关（调整后的危险比为1.98；95%置信区间为1.45-2.70；P 结论：白细胞介素（IL-12）和IL-8折叠变化与较高的客观反应率（ORR）相关：全面的血清生物标志物分析表明，在接受阿特珠单抗预处理的晚期NSCLC患者中，血清IL-8的折叠变化越小，预后越好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.