Oncotarget

Research Papers:

Prognostic value of the neutrophil-to-lymphocyte ratio in the ARQ 197-215 second-line study for advanced hepatocellular carcinoma

Nicola Personeni _, Laura Giordano, Giovanni Abbadessa, Camillo Porta, Ivan Borbath, Bruno Daniele, Jean-Luc Van Laethem, Hans Van Vlierberghe, Jörg Trojan, Enrico N. De Toni, Antonio Gasbarrini, Monica Lencioni, Maria E. Lamar, Yunxia Wang, Dale Shuster, Brian Schwartz, Armando Santoro and Lorenza Rimassa

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Oncotarget. 2017; 8:14408-14415. https://doi.org/10.18632/oncotarget.14797

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Abstract

Nicola Personeni1,2, Laura Giordano1, Giovanni Abbadessa3, Camillo Porta4, Ivan Borbath5, Bruno Daniele6, Jean-Luc Van Laethem7, Hans Van Vlierberghe8, Jörg Trojan9, Enrico N. De Toni10, Antonio Gasbarrini11, Monica Lencioni12, Maria E. Lamar3, Yunxia Wang3, Dale Shuster13, Brian Schwartz3, Armando Santoro1,14 and Lorenza Rimassa1

1 Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, MI, Italy

2 Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

3 Clinical Development & Translational Medicine, ArQule, Burlington, MA, United States

4 Fondazione IRCCS Policlinico Universitario San Matteo, Pavia, Italy

5 Cliniques Universitaires Saint-Luc, Brussels, Belgium

6 G. Rummo Hospital, Benevento, Italy

7 Erasme University Hospital, Brussels, Belgium

8 Ghent University Hospital, Gent, Belgium

9 Internal Medicine, J. W. Goethe University Hospital, Frankfurt, Germany

10 Klinikum der Universitaet Muenchen-Grosshadern, Munich, Germany

11 Policlinico Universitario Agostino Gemelli, Rome, Italy

12 Azienda Ospedaliero-Universitaria di Pisa, Pisa, Italy

13 Clinical Development, Daiichi-Sankyo, Edison, NJ, United States

14 Humanitas University, Rozzano, MI, Italy

Correspondence to:

Nicola Personeni, email:

Keywords: hepatocellular carcinoma; neutrophils; neutrophil-to-lymphocyte ratio; tivantinib; MET

Received: January 09, 2017 Accepted: January 11, 2017 Published: January 22, 2017

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.


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