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

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; Shintaro Nakagawa; Tetsuya Mitsudomi

doi:10.1016/j.lungcan.2024.108017

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

Lung Cancer. 2024 Nov 9:198:108017. doi: 10.1016/j.lungcan.2024.108017. Online ahead of print.

Authors

Hiroaki Akamatsu¹, Yasuhiro Koh², Makoto Nishio³, Yasushi Goto⁴, Hidetoshi Hayashi⁵, Satoru Miura⁶, Koji Tamada⁷, Hiroshi Kagamu⁸, Akihiko Gemma⁹, Ichiro Yoshino¹⁰, Toshihiro Misumi¹¹, Atsuto Mouri⁸, Ryota Saito¹², Naoto Takase¹³, Noriko Yanagitani³, Hiroshi Nokihara¹⁴, Masahiro Seike⁹, Kei Takamura¹⁵, Masahide Mori¹⁶, Shunichiro Iwasawa¹⁷, Shintaro Nakagawa¹⁷, Tetsuya Mitsudomi¹⁸

Affiliations

¹ Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
² Internal Medicine III, Wakayama Medical University, Wakayama, Japan; Center for Biomedical Sciences, CIMS, Wakayama Medical University, Wakayama, Japan.
³ Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
⁴ Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁵ Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan.
⁶ Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
⁷ Department of Immunology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
⁸ Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan.
⁹ Department of Pulmonary Medicine and Oncology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan.
¹⁰ Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
¹¹ Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan.
¹² Department of Respiratory Medicine, Tohoku University Hospital, Miyagi, Japan.
¹³ Department of Medical Oncology, Takarazuka City Hospital, Hyogo, Japan.
¹⁴ Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
¹⁵ Department of Respiratory Medicine, Obihiro-Kosei General Hospital, Hokkaido, Japan.
¹⁶ Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center, Osaka, Japan.
¹⁷ Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
¹⁸ Kindai Hospital Global Research Alliance Center and Thoracic Surgery, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Electronic address: mitsudom@med.kindai.ac.jp.

PMID: 39571250
DOI: 10.1016/j.lungcan.2024.108017

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.

Keywords: Atezolizumab; Chemokine; Cytokine; Immune checkpoint inhibitor; Interleukin-8; Non-small cell lung cancer.