Frontiers in immunology · 2026
C-reactive protein flare-response predicts the efficacy of PD-1 inhibitors in metastatic gastric cancer.
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Lei Yi-Hui, Zheng Hui, Song Xin-Fu, Wang Ya-Yue, Cai Feng-Bin
Аннотация
BACKGROUND: Currently, predictive biomarkers for the efficacy of immunotherapy in metastatic gastric cancer (mGC) during the era of immune checkpoint inhibitors are still under evaluation. The aim of this study is to investigate the predictive value of early C-reactive protein (CRP) kinetics on the efficacy of programmed cell death protein-1(PD-1) inhibitors in mGC patients with microsatellite stable (MSS).
METHODS: This retrospective study included 59 mGC patients with MSS who had been treated with PD-1 inhibitors as first-line therapy at a tertiary hospital. Based on the "CRP-flare response phenomenon," the patients were classified into three groups: CRP flare-responders, CRP responders, and non-CRP responders. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while the secondary endpoints included objective response rate.
RESULTS: Among the 59 patients, 21 were classified as CRP flare-responders, 18 as CRP responders, and 20 as non-CRP responders. The objective response rate for CRP flare-responders, CRP responders, and non-CRP responders were 38.1%, 16.7%, and 5.0% (p=0.031), respectively. The median OS of the CRP flare-responders, CRP responders, and non-CRP responders were 25.8 months, 16.3 months, and 11.9 months (p=0.0009), respectively. The median PFS of the CRP flare-responders, CRP responders, and non-CRP responders were 16.6 months, 6.8 months, and 5.1 months (p=0.0002), respectively. Both univariable and multivariable analyses demonstrated that CRP flare-responders had a significantly higher objective response rate and a lower risk of death compared with non-CRP responders (p < 0.05). Moreover, CRP flare-responders showed a significantly lower risk of disease progression compared with both CRP responders and non-CRP responders (p < 0.05).
CONCLUSIONS: Among patients with MSS mGC receiving first-line PD-1 inhibitor therapy, CRP flare response was associated with improved objective response, PFS, and OS. Early CRP kinetics may represent a promising predictive biomarker for immunotherapy efficacy in MSS mGC. Further large-scale prospective studies are warranted to validate these findings.
METHODS: This retrospective study included 59 mGC patients with MSS who had been treated with PD-1 inhibitors as first-line therapy at a tertiary hospital. Based on the "CRP-flare response phenomenon," the patients were classified into three groups: CRP flare-responders, CRP responders, and non-CRP responders. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while the secondary endpoints included objective response rate.
RESULTS: Among the 59 patients, 21 were classified as CRP flare-responders, 18 as CRP responders, and 20 as non-CRP responders. The objective response rate for CRP flare-responders, CRP responders, and non-CRP responders were 38.1%, 16.7%, and 5.0% (p=0.031), respectively. The median OS of the CRP flare-responders, CRP responders, and non-CRP responders were 25.8 months, 16.3 months, and 11.9 months (p=0.0009), respectively. The median PFS of the CRP flare-responders, CRP responders, and non-CRP responders were 16.6 months, 6.8 months, and 5.1 months (p=0.0002), respectively. Both univariable and multivariable analyses demonstrated that CRP flare-responders had a significantly higher objective response rate and a lower risk of death compared with non-CRP responders (p < 0.05). Moreover, CRP flare-responders showed a significantly lower risk of disease progression compared with both CRP responders and non-CRP responders (p < 0.05).
CONCLUSIONS: Among patients with MSS mGC receiving first-line PD-1 inhibitor therapy, CRP flare response was associated with improved objective response, PFS, and OS. Early CRP kinetics may represent a promising predictive biomarker for immunotherapy efficacy in MSS mGC. Further large-scale prospective studies are warranted to validate these findings.