Evaluation of early C‐reactive protein kinetics as an early response marker in biliary tract cancer treated with combined chemoimmunotherapy: A multicenter observational study

BACKGROUND: Reliable prognostic biomarkers for treatment response in patients with biliary tract cancer (BTC) who receive chemoimmunotherapy are still lacking. The objective of this study was to evaluate the potential of early C-reactive protein (CRP) kinetics as a tool for predicting survival in these patients. METHODS: The authors retrospectively analyzed patients with BTC who received chemoimmunotherapy at eight tertiary centers and evaluated CRP kinetic models with regard of their prognostic ability within the first 3 months of treatment. RESULTS: Progression-free survival (PFS) and overall survival (OS) differed according to CRP dynamics. The median PFS was not reached (95% confidence interval [CI], not reached to not reached) for patients with consistently normal CRP, 11.0 months (95% CI, 6.7-15.3 months) for those with initially normal CRP, 6.0 months (95% CI, 3.6-8.4 months) for those with subsequent CRP normalization, and 2.0 months (95% CI, 0.9-3.1 months) for those with persistently elevated CRP. The corresponding median OS was not reached (95% CI, not reached to not reached) for patients with consistently normal CRP, 26 months (95% CI,15.5-36.5 months) for those with initially normal CRP, 23 months (95% CI, 12.0-34.0 months) for those with subsequent normalization, and 9.0 months (95% CI, 6.3-11.7 months) for those with persistently elevated CRP (PFS, log-rank p < .001; OS, p = .005). The overall response rates were 50%, 33.3%, 36.0%, and 21.2%, respectively. The prognostic performance of this model remained stable when subgroup definitions were based on 6-week cutoffs. CONCLUSIONS: CRP kinetics may be a valuable prognostic tool for early response assessment in patients with BTC who receive chemoimmunotherapy. However, these findings require prospective external validation in larger cohorts.