Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands: An Analysis of Toxicity, Efficacy, and Predictive Markers.
Advanced renal cancer
Immune checkpoint inhibitor
Metastatic
Second-line therapy
Systemic therapy
Journal
Clinical genitourinary cancer
ISSN: 1938-0682
Titre abrégé: Clin Genitourin Cancer
Pays: United States
ID NLM: 101260955
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
29
08
2020
revised:
05
10
2020
accepted:
10
10
2020
pubmed:
16
12
2020
medline:
19
8
2021
entrez:
15
12
2020
Statut:
ppublish
Résumé
Nivolumab, a programmed death 1 inhibitor, has been approved as second-line 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. 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. 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 non-clear-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 12-months 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). 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.
Sections du résumé
BACKGROUND
Nivolumab, a programmed death 1 inhibitor, has been approved as second-line 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 non-clear-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 12-months 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.
Identifiants
pubmed: 33317946
pii: S1558-7673(20)30230-5
doi: 10.1016/j.clgc.2020.10.003
pii:
doi:
Substances chimiques
Biomarkers
0
Nivolumab
31YO63LBSN
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
274.e1-274.e16Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.