Prognostic value of systemic inflammation markers in advanced esophageal squamous cell carcinoma treated with second-line nivolumab: a real-world European study

Nivolumab is a standard second-line therapy for advanced esophageal squamous cell carcinoma (ESCC), based on pivotal phase III trials largely conducted in Asian populations. Real-world evidence in Western patients remains limited. Systemic inflammation- and nutrition-based indices have been proposed as prognostic biomarkers in immunotherapy but remain scarcely validated in ESCC. We conducted a retrospective multicenter study across six institutions of the Galician Research Group on Gastrointestinal Tumors (GITuD). Eligible patients had histologically confirmed advanced or unresectable ESCC progressing after platinum-based chemotherapy or within six months of curative-intent therapy. All patients received nivolumab monotherapy between April 2019 and January 2023. Clinical outcomes were assessed using RECIST v1.1 and Kaplan–Meier estimates. Prognostic indices included NLR, PLR, SII, LDH, albumin, NAR, GIPI, and GRIm. Cut-off values for NLR, PLR, SII, and NAR were derived from cohort-specific ROC analyses and should be considered exploratory. NLR, PLR, SII, and NAR were additionally evaluated as continuous covariates. GIPI and GRIm were assessed in separate multivariable Cox models adjusted for ECOG PS and rapid-progressor status. Forty-five patients were included. Median age was 60.9 years, 80% were male, and 26.7% had ECOG PS 2. Rapid progressors accounted for 35.6% of the cohort. The objective response rate was 17.8% and disease control rate was 40.0%. After median follow-up of 37 months, median overall survival was 9.66 months (95% CI, 5.49–15.64) and progression-free survival 3.38 months (95% CI, 2.63–5.26). In univariate categorical analyses, NLR, SII, NAR, and GRIm were significantly associated with overall survival. When evaluated as continuous covariates, NLR and NAR remained significantly associated with overall survival, whereas PLR and SII did not. In separate multivariable models adjusted for ECOG PS and rapid-progressor status, both GRIm and GIPI were significantly associated with overall survival. No indices were significantly associated with progression-free survival. Safety findings were consistent with the known safety profile of nivolumab. Clinical outcomes associated with second-line nivolumab in this European real-world cohort were broadly consistent with those reported in pivotal clinical trials. Several systemic inflammation- and nutrition-based indices showed exploratory associations with overall survival, including GIPI and GRIm in separate clinically adjusted multivariable models. These findings require validation in larger independent cohorts.