C-reactive protein kinetics as a predictive marker for long-term outcome of immune checkpoint inhibitors in oesophagogastric cancer

Abstract

Abstract Background The treatment efficacy of immune checkpoint inhibitors (ICIs) is limited, and biomarkers that identify responders are urgently needed. We investigated whether C-reactive protein (CRP) kinetics are associated with the treatment efficacy of ICIs and prognosis in oesophagogastric cancers. Methods We analysed 76 gastric cancer patients treated with nivolumab monotherapy. Patients were classified as CRP-spike, CRP-flat or CRP-increase according to CRP kinetics within 6 weeks after nivolumab initiation, and the treatment response and prognosis were compared. We further validated this classification in 71 oesophageal cancer patients with nivolumab monotherapy. Results In the gastric cancer cohort, the CRP-spike, CRP-flat, and CRP-increase subgroups included 9, 37 and 30 patients, respectively. The CRP-spike subgroup had higher disease control rates than the CRP-increase subgroup (P = 0.0068) and had significantly better progression-free survival (PFS) (vs. CRP-flat: P = 0.045, CRP-increase: P = 0.0001). Multivariate analysis for PFS identified CRP-spike (HR = 0.38, P = 0.029) as an independent favourable prognostic factor. In the oesophageal cancer cohort, the CRP-spike, CRP-flat, and CRP-increase subgroups included 13, 27 and 31 patients, respectively, and multivariate analysis for PFS also identified CRP-spike (HR = 0.28, P = 0.0044) as an independent favourable prognostic factor. Conclusions CRP kinetics may be useful in predicting the long-term outcome of nivolumab treatment in oesophagogastric cancers.