title: Prognostic value of the neutrophil-to-lymphocyte ratio in the ARQ 197-215 second-line study for advanced hepatocellular carcinoma.
abstract: The ARQ 197-215 study randomized patients to tivantinib or placebo and pre-specified efficacy analyses indicated the predictive value of MET expression as a marker of benefit from tivantinib in hepatocellular carcinoma (HCC). We aimed to explore the neutrophil-to-lymphocyte ratio (NLR) in 98 ARQ 197-215 patients with available absolute neutrophil count and absolute lymphocyte count at baseline. The cut-off value used to define high versus low NLR was 3.0. In univariate analysis, high NLR was associated with hazard ratio (HR) for overall survival (OS) of 1.58 [95% confidence interval (CI) 1.01; 2.47; P <0.046], corresponding to median OS of 5.1 months versus 7.8 months in patients with low NLR (P = 0.044). In contrast, time to progression was not significantly affected by NLR (P = 0.20). Multivariable model confirmed that both NLR >3 (P = 0.03) and presence of vascular invasion (P = 0.017) were negatively associated with OS. After adjustment for vascular invasion, NLR independently predicted survival in both the placebo and the tivantinib cohort. For OS, no interaction was detected between NLR status and treatment (Pinteraction = 0.40). Baseline NLR is an independent prognostic biomarker in patients with HCC and compensated liver function who are candidate for second-line treatments.
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Personeni
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giordano
authors.affiliation: Clinical Development & Translational Medicine, ArQule, Burlington, MA, United States.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abbadessa
authors.affiliation: Fondazione IRCCS Policlinico Universitario San Matteo, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borbath
authors.affiliation: G. Rummo Hospital, Benevento, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Daniele
authors.affiliation: Erasme University Hospital, Brussels, Belgium.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Van Laethem
authors.affiliation: Ghent University Hospital, Gent, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.affiliation: Internal Medicine, J. W. Goethe University Hospital, Frankfurt, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Trojan
authors.affiliation: Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany.
authors.forename: Enrico N
authors.initials: EN
authors.lastname: De Toni
authors.affiliation: Policlinico Universitario Agostino Gemelli, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.affiliation: Azienda Ospedaliero-Universitaria di Pisa, Pisa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Lencioni
authors.affiliation: Clinical Development & Translational Medicine, ArQule, Burlington, MA, United States.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Lamar
authors.affiliation: Clinical Development & Translational Medicine, ArQule, Burlington, MA, United States.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Development, Daiichi-Sankyo, Edison, NJ, United States.
authors.forename: Dale
authors.initials: D
authors.lastname: Shuster
authors.affiliation: Clinical Development & Translational Medicine, ArQule, Burlington, MA, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Schwartz
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.|Humanitas University, Rozzano, Milan, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Rimassa
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009504:Neutrophils / Q000473:pathology*; D011379:Prognosis; D011760:Pyrrolidinones / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: C551661:ARQ 197; D011760:Pyrrolidinones; D011804:Quinolines
keywords: MET; hepatocellular carcinoma; neutrophil-to-lymphocyte ratio; neutrophils; tivantinib