C-reactive protein flare-response predicts the efficacy of PD-1/PD-L1 monoclonal antibodies in metastatic gastric cancer

Abstract

Currently, predictive biomarkers for the efficacy of immunotherapy in metastatic gastric cancer (mGC) during the era of immune checkpoint inhibitorsare still under evaluation. This retrospective study investigated the predictive value of early C-reactive protein (CRP) kinetics on the efficacy of programmed cell death protein-1(PD-1)/programmed cell death ligand 1 (PD-L1)monoclonal antibody treatment in mGC. A total of 42 mGC patients included in this study, who treated with PD-1/PD-L1 monoclonal antibodies between 2019 and 2022. Based on early CRP kinetics, patients were categorized into three groups: CRP flare-responders: those whose CRP levels increased to more than twice the baseline within one month of initiating PD-1/PD-L1 monoclonal antibodies and then decreased to below baseline within three months; (2) CRP responders: those whose CRP levels decreased by ≥30% within three months of treatment; (3) non-CRP responders: the remaining patients. The objective response rates for CRP flare-responders, CRP responders, and non-CRP responders were 57.1%, 26.6%, and 7.7%(p=0.042), respectively. The median overall survivals (OS) of the CRP flare-responder, CRP responder, and non-CRP responder groups were not reached, not reached, and 11.9 months(p=0.006), respectively. The median progression-free survivals (PFS) of the CRP flare-responder, CRP responder, and non-CRP responder groups were not reached, 8 months, and 4.5 months (p=0.003), respectively. Multivariate analysis revealed that early CRP kinetics were independent predictors of objective response (p=0.033), OS (p=0.026), and PFS (p=0.004). Our study showed that in mGC patients receiving PD-1/PD-L1 monoclonal antibody therapy, CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes. Early CRP kinetics have predictive value for the therapeutic efficacy of PD-1/PD-L1 monoclonal antibodies.