Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands: An Analysis of Toxicity, Efficacy, and Predictive Markers

Nivolumab has been approved as second-line treatment for advanced renal cell carcinoma in Europe. We performed a real-world analysis to validate this practice. The study included 264 patients from 24 hospitals in the Netherlands. We found that toxicity and efficacy of nivolumab are comparable with previous results. Increase in eosinophil count was the strongest predictor of improved survival. Results can be used to improve personalized therapy. Background: Nivolumab, a programmed death 1 inhibitor, has been approved as secondline treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. Patients and Methods: This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The 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 International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had >= 3 lines of previous therapy, 7% had noneclear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P=.038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P=.000). On-treatment increase in eosinophils by week 8 predicted improved OS (P=.003), PFS (P=.000), and TTF (P=.014), whereas a decrease of neutrophils was associated with significantly better TTF (P=.023). Conclusions: The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation. (C) 2020 Elsevier Inc. All rights reserved.