Medizinische Universität Graz - Research portal
Selected Publication:
Sandner, A.
Predictive biomarkers in cancer patients receiving immune checkpoint inhibitors:
Early C-reactive protein kinetics as a prognostic and predictive marker for response and survival in a multi-cancer collective
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 74
[OPEN ACCESS]
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- Authors Med Uni Graz:
- Advisor:
- Terbuch Angelika
- Altmetrics:
- Abstract:
- Background Recently, early C-reactive protein (CRP) kinetics have been suggested as biomarkers predicting the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The aim of this study was to validate the accuracy of early CRP kinetics for the prediction of ICI efficacy in a large multi-cancer cohort. Methods 562 patients with solid malignancies undergoing palliative ICI treatment at two Austrian hospitals formed the studied cohort. In a first step, the patients were classified by their specific longitudinal serum CRP response patterns during the first three months after ICI treatment initiation according to the previously defined three-group model by Fukuda et al., 2021, and its accuracy was analysed. In a second step, the established CRP kinetics model was expanded by a fourth pattern of CRP kinetics. The refined four-group model (CRP-flare responders, CRP responders, CRP non-responders, all-normal CRP) was evaluated regarding its prognostic and predictive accuracy. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were defined as co-primary endpoints. Uni-and multivariable logistic regression models, Landmark analysis and Cox-proportional hazard models including CRP kinetics as time-dependent variable were implemented. Results The ORR in patients with all-normal CRP, CRP responders, CRP flare-responders and CRP non-responders was 41%, 38%, 31% and 12%, respectively. The median OS and PFS estimates were 24.5 months (95%CI 18.5 – not reached) and 8.2 months (95%CI 5.9-12.0) in patients with all-normal CRP, 16.1 months (95%CI 12.6-19.8) and 6.1 months (95%CI 4.9-7.2) in CRP-responders, 14.0 months (95%CI 8.5-19.4) and 5.7 months (95%CI 4.1-8.5) in CRP flare-responders and 8.1 months (95%CI 5.8-9.9) and 2.3 months (95%CI 2.2-2.8) in CRP non-responders (log-rank p for PFS and OS <0.001). These findings prevailed in multivariable analysis. The prognostic and predictive value of the established three-group model for early CRP kinetics by Fukuda et al. could be confirmed and refined by means of the extended four-group model. Conclusion Early on-treatment CRP kinetics represent an accurate biomarker for early prediction of treatment response, progression risk and clinical outcome in patients undergoing ICI therapy across various solid cancer entities.