194P - Early kinetics of C-reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: A multi-center cohort study

Background

C-reactive protein (CRP) kinetics have recently been suggested as predictive biomarkers for the efficacy of immune checkpoint inhibitor (ICI) therapy in selected cancer types. The aim of this study was to characterize early CRP kinetics as a tumor-agnostic biomarker for ICI treatment outcomes.

Methods

In this multicenter retrospective cohort study, two independent cohorts of patients with various cancer types undergoing palliative ICI treatment at Austrian academic centers served as the discovery (n=562) and validation cohort (n=474). Four different patterns of CRP-kinetics in the first 3 months of ICI therapy were defined (CRP-flare responders, CRP-responders, CRP non-responders, patients with all-normal CRP). Objective response rate (ORR), progression-free- (PFS) and overall survival (OS) were defined as co-primary endpoints. Uni-and multivariable logistic regression, Landmark analysis and Cox-regression including CRP kinetics as time-dependent variable were performed.

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 and could be fully confirmed in our validation cohort. Pooled subgroup analysis suggested a consistent predictive significance of early CRP kinetics for treatment efficacy and outcome independent of cancer type.

Conclusions

Early CRP kinetics represent a tumor-agnostic predictor for treatment response, progression risk and mortality in patients with cancer undergoing ICI therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research was supported by a research grant from AstraZeneca GmbH , Bristol Myers Squibb GesmbH (BMS), Merck Sharp & Dohme Ges.m.b.H., Roche Austria GmbH and Sanofi-aventis GmbH. The hypothesis of this study was not suggested by the the funding body, which had no role in the design, analysis, and publication of this study. MP (Matthias Preusser) gratefully acknowledges financial support from the Austrian Federal Ministry for Digital and Economic Affairs, the Austrian National Foundation for Research, Technology and Development and the Christian Doppler Research Association.

Disclosure

D. Barth: Financial Interests, Personal, Advisory Board: Roche, MSD, EISAI. F. Moik: Financial Interests, Personal, Advisory Board: Servier, BMS. L. Koch: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Sanofi Aventis. E. Richtig: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, BMS, MSD, Merck, Novartis, Puerre Fabre, Sanofi Aventis; Financial Interests, Personal, Steering Committee Member: Novartis. M. Preusser: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, BMS, Novartis, Gerson Lehrman Group, CMC Contrast, GSK, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, MSD, Adastra, Tocagen, Gan & Lee Pharmaceuticals, Servier. J.M. Riedl: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD. All other authors have declared no conflicts of interest.