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Mehmet A. Bilen, Winship Cancer Institute of Emory University, 1365B Clifton Road NE, Suite B4000, Office 4212, Atlanta, GA 30322. Phone: 404–778–3693; E-mail: mehmet.a.bilen@emory.edu

M.A. Bilen: Conceptualization, investigation, methodology, writing–review and editing. B.I. Rini: Investigation, writing–review and editing. M.H. Voss: Investigation, writing–review and editing. J. Larkin: Investigation, writing–review and editing. J.B.A.G. Haanen: Investigation, writing–review and editing. L. Albiges: Investigation, writing–review and editing. L.C. Pagliaro: Investigation, writing–review and editing. E.G. Voog: Investigation, writing–review and editing. E.T. Lam: Investigation, writing–review and editing. N. Kislov: Investigation, writing–review and editing. B.A. McGregor: Investigation, writing–review and editing. A.-K.A. Lalani: Investigation, writing–review and editing. B. Huang: Conceptualization, formal analysis, supervision, investigation, methodology, writing–review and editing. A. di Pietro: Conceptualization, supervision, investigation, methodology, writing–review and editing. S. Krulewicz: Conceptualization, supervision, investigation, methodology, writing–review and editing. P.B. Robbins: Conceptualization, supervision, investigation, methodology, writing–review and editing. T.K. Choueiri: Conceptualization, investigation, methodology, writing–review and editing.

We thank the patients and their families, investigators, coinvestigators, and the study teams at each of the participating centers. This trial was sponsored by Pfizer as part of an alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). Expert bioinformatic support was provided by Xinmeng (Jasmine) Mu (Pfizer computational biology). Medical writing support was provided by Shilpa Lalchandani and Graeme Hacking of ClinicalThinking (Hamilton, NJ), and funded by Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany. B. Huang and P.B. Robbins had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

M.A. Bilen reports personal fees from Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, the healthcare business of Merck KGaA, Darmstadt, Germany, SeaGen, and Sanofi, and grants from Xencor, Bayer, BMS, Genentech/Roche, SeaGen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome and Company, AAA, Peloton Therapeutics, and Pfizer outside the submitted work. B.I. Rini reports grants, personal fees, and non-financial support from Pfizer during the conduct of the study as well as grants, personal fees, and non-financial support from Merck & Co., Kenilworth, NJ; personal fees from Exelixis; grants, personal fees, and non-financial support from BMS; and personal fees from Eisai outside the submitted work. M.H. Voss reports grants and personal fees from Pfizer during the conduct of the study as well as personal fees from AVEO, Eisai, Novartis, and Onquality; non-financial support from AstraZeneca; personal fees from Merck & Co., Kenilworth, NJ; grants from BMS; and personal fees from Calithera, Corvus, and Exelixis outside the submitted work. J. Larkin reports personal fees and other support from Roche and Novartis; personal fees from iOnctura; personal fees and other support from BMS and Pfizer; personal fees from Incyte, Dynavax, CRUK, GSK, Eisai, Merck & Co., Kenilworth, NJ, touchIME, touchExperts, Iovance, and Boston Biomedical; personal fees and other support from Immunocore; personal fees from YKT Global and Apple Tree; and other support from Achilles Therapeutics, Nektar Therapeutics, Covance, Pharmacyclics, and AVEO during the conduct of the study. J.B.A.G. Haanen reports other support from the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer during the conduct of the study as well as other support from Achilles Therapeutics, Immunocore, Instil Bio, and PokeAcel; grants from BioNTech; other support from T-knife; grants and personal fees from Neogene Therapeutics; grants from BMS, Amgen, Merck & Co., Kenilworth, NJ, Novartis, Asher Bio; and other support from Ipsen, Molecular Partners, Roche, Sanofi, and TRV outside the submitted work. L. Albiges reports other support from Pfizer, Novartis, BMS, Ipsen, Astellas, Merck & Co., Kenilworth, NJ, Janssen, AstraZeneca, and Eisai outside the submitted work. L.C. Pagliaro reports other support from Pfizer during the conduct of the study. E.T. Lam reports other support from Pfizer, Arrowhead, and BMS; personal fees and other support from Calithera Biosciences; and other support from Merck & Co., Kenilworth, NJ, and Roche during the conduct of the study. N. Kislov reports grants from Nektar during the conduct of the study as well as grants from AstraZeneca, Eisai, Exelixis, Merck & Co., Kenilworth, NJ, Genentech/Roche, and GSK; personal fees from Ipsen; and grants from Novartis outside the submitted work. B.A. McGregor reports grants and personal fees from Pfizer during the conduct of the study as well as personal fees from Astellas and SeaGen; grants and personal fees from BMS and Exelixis; personal fees from Eisai; grants and personal fees from Calithera; and personal fees from Dendreon, the healthcare business of Merck KGaA, Darmstadt, Germany, and Merck & Co., Kenilworth, NJ, outside the submitted work. A.-K.A. Lalani reports personal fees from Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche, and TerSera, and grants from BioCanRx, BMS, Novartis, Roche, Ipsen, and the healthcare business of Merck KGaA, Darmstadt, Germany outside the submitted work. B. Huang reports other support from Pfizer Inc. outside the submitted work. A. di Pietro reports employment with Pfizer. P.B. Robbins reports other support from Pfizer during the conduct of the study as well as other support from Pfizer outside the submitted work. T.K. Choueiri reports grants, personal fees, and non-financial support from AstraZeneca during the conduct of the study as well as other support from NCCN panel; personal fees from the Genitourinary Cancers Steering Committee of the National Cancer Institute; and personal fees from UpToDate outside the submitted work; and was an invited speaker at CME-related events (OncLive, Targeted Oncology, PER, Peerview, and others). No disclosures were reported by the other authors.

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Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • PRETREATMENT NEUTROPHIL
  • SUBSETS

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

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Journal Title:

CLINICAL CANCER RESEARCH

Volume:

Volume 28, Number 4

Publisher:

, Pages 738-747

Type of Work:

Article | Final Publisher PDF

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.
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