Association of Neutrophil-to-Lymphocyte Ratio with Efficacy of First-Line Avelumab plus Axitinib vs. Sunitinib in Patients with Advanced Renal Cell Carcinoma Enrolled in the Phase 3 JAVELIN Renal 101 Trial

• Type of Material: Article
• Authors: Mehmet Bilen, Emory University; Brian Rini, Vanderbilt University; Martin H Voss, Memorial Sloan Kettering Cancer Center; James Larkin, Royal Marsden NHS Foundation Trust; John BAG Haanen, Netherlands Cancer Institute; Laurence Albiges, Inst Gustave Roussy; Lance C Pagliaro, Mayo Clinic; Eric G Voog, Clinique Victor Hugo; Elaine T Lam, University of Colorado, Aurora; Nikolay Kislov, Yaroslavl Regional Clinical Oncological Hospital; Bradley A McGregor, Dana-Farber Cancer Institute; Aly-Khan A Lalani, Juravinski Cancer Center; Bo Huang, Pfizer, Groton, Connecticut; Alessandra di Pietro, Pfizer SRL; Stan Krulewicz, Pfizer; Paul B Robbins, Pfizer; Toni K Choueiri, Dana-Farber Cancer Institute
• Language: English
• Date: 2022-02-15
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: ©2021 The Authors; Published by the American Association for Cancer Research
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-21-1688
• Title of Journal or Parent Work: CLINICAL CANCER RESEARCH
• Volume: 28
• Issue: 4
• Start Page: 738
• End Page: 747
• Keywords: SUBSETS; Oncology; PRETREATMENT NEUTROPHIL; Life Sciences & Biomedicine; Science & Technology

Abstract

Purpose: To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and efficacy of avelumab plus axitinib or sunitinib. Experimental Design: Adult patients with untreated advanced renal cell carcinoma (RCC) with a clear-cell component, ≥1 measurable lesions, Eastern Cooperative Oncology Group performance status of 0 or 1, fresh or archival tumor specimen, and adequate renal, cardiac, and hepatic function were included. Retrospective analyses of the association between baseline NLR and progression-free survival (PFS) and overall survival (OS) in the avelumab plus axitinib or sunitinib arms were performed using the first interim analysis of the phase 3 JAVELIN Renal 101 trial (NCT02684006). Multivariate Cox regression analyses of PFS and OS were conducted. Translational data were assessed to elucidate the underlying biology associated with differences in NLR. Results: Patients with below-median NLR had longer observed PFS with avelumab plus axitinib [stratified HR, 0.85; 95% confidence interval (CI), 0.634-1.153] or sunitinib (HR, 0.56; 95% CI, 0.415-0.745). In the avelumab plus axitinib or sunitinib arms, respectively, median PFS was 13.8 and 11.2 months in patients with below-median NLR, and 13.3 and 5.6 months in patients with median-or-higher NLR. Below-median NLR was also associated with longer observed OS in the avelumab plus axitinib (HR, 0.51; 95% CI, 0.300-0.871) and sunitinib arms (HR, 0.30; 95% CI, 0.174-0.511). Tumor analyses showed an association between NLR and key biological characteristics, suggesting a role of NLR in underlying mechanisms influencing clinical outcome. Conclusions: Current data support NLR as a prognostic biomarker in patients with advanced RCC receiving avelumab plus axitinib or sunitinib.