Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study

Xinlong Zheng; Longfeng Zhang; Lin Wu; Jun Zhao; Jianguo Sun; Yong Fang; Jin Zhou; Qian Chu; Yihong Shen; Zhenzhou Yang; Lijin Chen; Meijuan Huang; Xiaoyan Lin; Zhenhua Liu; Peng Shen; Zhijie Wang; Xin Wang; Huijuan Wang; Zhengbo Han; Anwen Liu; Hongmei Zhang; Feng Ye; Wen Gao; Fang Wu; Zhengbo Song; Shengchi Chen; Chenzhi Zhou; Qian Wang; Chunwei Xu; Dingzhi Huang; Xiaobin Zheng; Qian Miao; Kan Jiang; Yiquan Xu; Shiwen Wu; Haibo Wang; Qiuyu Zhang; Shanshan Yang; Yujing Li; Sihui Chen; Gen Lin

doi:10.1186/s12885-023-11737-x

Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study

BMC Cancer. 2023 Dec 16;23(1):1244. doi: 10.1186/s12885-023-11737-x.

Authors

Xinlong Zheng^#¹, Longfeng Zhang^#¹, Lin Wu^#², Jun Zhao^#³, Jianguo Sun^#⁴, Yong Fang⁵, Jin Zhou⁶, Qian Chu⁷, Yihong Shen⁸, Zhenzhou Yang⁹, Lijin Chen¹⁰, Meijuan Huang¹¹, Xiaoyan Lin¹², Zhenhua Liu¹³, Peng Shen¹⁴, Zhijie Wang¹⁵, Xin Wang¹⁶, Huijuan Wang¹⁷, Zhengbo Han¹⁸, Anwen Liu¹⁹, Hongmei Zhang²⁰, Feng Ye²¹, Wen Gao²², Fang Wu²³, Zhengbo Song²⁴, Shengchi Chen²⁵, Chenzhi Zhou²⁶, Qian Wang²⁷, Chunwei Xu²⁸, Dingzhi Huang²⁹, Xiaobin Zheng¹, Qian Miao¹, Kan Jiang¹, Yiquan Xu¹, Shiwen Wu¹, Haibo Wang¹, Qiuyu Zhang³⁰, Shanshan Yang¹, Yujing Li¹, Sihui Chen¹, Gen Lin^{31

32

33}

Affiliations

¹ Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
² The Second Department of Thoracic Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China.
³ Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
⁴ Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China.
⁵ Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang, China.
⁶ School of Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁷ Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁸ Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁹ Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
¹⁰ Department of Oncology, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, China.
¹¹ Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
¹² Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
¹³ Department of Medical Oncology, Provincial Clinical College, Fujian Medical University, Fujian provincial hospital, Fuzhou, China.
¹⁴ Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
¹⁵ Medical Oncology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.
¹⁶ Department of Oncology, Zhongshan Hospital of Xiamen University, Xiamen, China.
¹⁷ Department of Respiratory Medicine, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
¹⁸ Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
¹⁹ Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
²⁰ Department of Oncology, Xijing Hospital, Airforce Military Medical University, Xian, Shanxi, China.
²¹ Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China.
²² Department of Medical Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
²³ Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
²⁴ Department of Clinical Trial, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
²⁵ Department of Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, China.
²⁶ Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
²⁷ Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
²⁸ Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University Nanjing, Nanjing, Jiangsu, China.
²⁹ Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
³⁰ Institute of Immunotherapy, Fujian Medical University, Fuzhou, China.
³¹ Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. fjzllg133@fjzlhospital.com.
³² Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China. fjzllg133@fjzlhospital.com.
³³ Interdisciplinary Institute for Medical Engineering, Fuzhou University, Fuzhou, China. fjzllg133@fjzlhospital.com.

^# Contributed equally.

Abstract

Aims: To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC).

Materials and methods: In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups.

Results: Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033).

Conclusion: In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Keywords: C-reactive protein; Immune checkpoint inhibitors; Lung squamous cell carcinoma; Predictive biomarker.

Publication types

Multicenter Study

MeSH terms

C-Reactive Protein
Carcinoma, Non-Small-Cell Lung*
Carcinoma, Squamous Cell* / drug therapy
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Lung
Lung Neoplasms* / drug therapy
Retrospective Studies

Substances

C-Reactive Protein
Immune Checkpoint Inhibitors