Real World Data of Nivolumab for Advanced Renal-Cell Carcinoma Patients in the Netherlands: An analysis of toxicity, efficacy and predictive markers

Abstract Background Nivolumab, a programmed death (PD) 1 inhibitor, has been approved as second line treatment for advanced renal-cell carcinoma (RCC) in Europe since 2016. We investigated toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. Methods A retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. Main outcome parameters included toxicity, objective response rate(ORR), overall survival(OS), progression-free survival (PFS), time to progression(TTP) and time to treatment failure(TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated. Results Data on 264 patients were available, of whom 42% were IMDC poor-risk at start of nivolumab, 16% had > 3 lines of previous therapy, 7% non-clear-cell, 11% brain metastases and 20% were previously treated with everolimus. Grade 3-4 immune related adverse events (irAE) occurred in 15%. The median OS was 18.7 months (95% CI,13.7–23.7). Progression occurred in 170 of 264 patients (64.4%) with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. ORR was 18.6% (49 of 264, 95% CI, 14-23). Elevated baseline lymphocytes were associated with improved PFS (P=0.038) and elevated baseline LDH with poor OS, PFS and TTF(P=0.000). On-treatment increase in eosinophils by week 8 predicted improved OS(P=0.003), PFS(P=0.000) and TTF(P=0.014), while a decrease of neutrophils was associated with significantly better TTF(P=0.023). Conclusions Toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable to the results in the pivotal phase 3 and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation.