Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort

Abstract Background Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. Methods This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. Results Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events ( P < .0001), including rash ( P < .0001), hypothyroidism ( P = .03), and interstitial pneumonia ( P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs ( P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil–lymphocyte ratio ( P = .001), and PMI ( P = .024) were significant. Multivariate analysis further identified CAR hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15–2.25, P = .0053) in addition to PS (HR = 1.65, 95% CI 1.23–2.22, P = .0008) as independent prognostic parameters. Conclusions CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. Trial Registration UMIN000040462