Akamatsu Hiroaki, Koh Yasuhiro, Nishio Makoto, Goto Yasushi, Hayashi Hidetoshi, Miura Satoru, Tamada Koji, Kagamu Hiroshi, Gemma Akihiko, Yoshino Ichiro, Misumi Toshihiro, Mouri Atsuto, Saito Ryota, Takase Naoto, Yanagitani Noriko, Nokihara Hiroshi, Seike Masahiro, Takamura Kei, Mori Masahide, Iwasawa Shunichiro, Nakagawa Shintaro, Mitsudomi Tetsuya
Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Internal Medicine III, Wakayama Medical University, Wakayama, Japan; Center for Biomedical Sciences, CIMS, Wakayama Medical University, Wakayama, Japan.
Lung Cancer. 2024 Dec;198:108017. doi: 10.1016/j.lungcan.2024.108017. Epub 2024 Nov 9.
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.
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.
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.
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.
程序性细胞死亡配体1（PD-L1）表达尽管存在缺陷，但仍被广泛用于预测PD-(L)1抑制剂的疗效。先前的研究提出了多种血清生物标志物的应用；然而，由于样本量有限或这些研究中许多仅关注单一生物标志物，研究结果尚无定论。本研究分析了多种血清生物标志物，以探讨其在现实环境中接受PD-L1抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者大样本队列中的预测能力。
这是J-TAIL研究的一项子研究，J-TAIL是一项关于阿替利珠单抗单药治疗经治晚期NSCLC患者的前瞻性观察性研究。2019年4月至10月，从日本73个地点招募了262例患者。在基线和阿替利珠单抗第二剂给药时采集血清样本。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分析。研究了第二剂给药时相对于基线的基线值和变化倍数与阿替利珠单抗疗效的相关性。
在评估的51种蛋白质中，较高的基线白细胞介素（IL）-12水平、较高的可溶性CD40配体变化倍数、较低的IL-8变化倍数与较高的客观缓解率（ORR）相关。其中，只有较低的IL-8变化倍数与更好的无进展生存期（PFS）相关（调整后风险比，1.98；95%置信区间，1.45-2.70；P<0.01）。多变量分析表明，较低的IL-8变化倍数是ORR和PFS的独立因素。IL-8变化倍数与中性粒细胞/淋巴细胞比值无关，两者均低的患者观察到持久的PFS。
综合血清生物标志物分析显示，血清IL-8变化倍数较低与接受阿替利珠单抗治疗的经治晚期NSCLC患者的更好结局相关。
