Evaluation of early C-reactive protein kinetics as an early response marker in biliary tract cancer patients treated with combined chemoimmunotherapy.

530 Background: Reliable prognostic biomarkers for treatment response in advanced biliary tract cancer (BTC) patients receiving chemoimmunotherapy are still lacking. The aim of this study was to evaluate early c-reactive protein CRP kinetics potential for survival prediction in these patients. Methods: All patients with BTC starting Durvalumab treatment between January 2022 and December 2023 at eight national tertiary centers were retrospectively analyzed and the predictive ability of the CRP kinetics within the first three months was evaluated. Patients were divided into four groups according to their CRP kinetics: The “normal” group, with initial CRP values below the upper limit of normal at treatment initiation, the “all-normal” group, with consistently normal CRP values within the first three months, the “normalized” group, with initially elevated CRP values that normalized and the “non-normalized” group, with the other patients. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS) and overall response rate (ORR) were secondary endpoints. Univariable and multivariable logistic regression, Cox regression and Kaplan-Meier survival analysis were performed. Results: Of the 104 eligible patients 6, 36, 26 and 36 patients were allocated to the “all-normal”, “normal”, “normalized” and “non-normalized” groups, respectively. The groups did not differ in regard of gender, age, tumor subtype, stage or performance index. PFS and OS were “not reached” (95%-CI “not reached” – “not reached”) and “not reached” (95%-CI “not reached” – “not reached”) in the all-normal group, 11.5 months (95%-CI 3.9 – 19.2 months) and “not reached” (95%-CI “not reached” – “not reached”) in the “normal” group, 12.4 months (95%-CI 4.4 – 20.4 months) and 21 months (95%-CI “not reached” – “not reached”) in the “normalized” group, and 3.1 months (95%-CI 1.2– 5.0 months) and 9.2 months (95%-CI 7.7– 10.8 months) in the “non-normalized"(log rank for PFS and OS <0.001). The overall response rates were 50%, 33.3%, 36.0% and 21.2%, respectively. Predictive power of this model remained consistent, when the definition cut-offs of subgroups were set at six weeks. Conclusions: Early CRP kinetics may be a valuable predictive tool for early response assessment in BTC patients receiving chemoimmunotherapy and can be applied within six weeks after treatment initiation, thereby allowing early treatment adjustment. Since longitudinal assessment of CRP values is cheap and easy-to-measure it should be implemented in routine BTC managements.