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.
Highlights
Hepatocellular carcinoma (HCC) accounts for nearly 80% of primary liver cancer cases [1] and it is a leading cause of death worldwide [2]
The survival differences attributed to neutrophil-to-lymphocyte ratio (NLR) status are substantial, in light of the survival outcomes reported in the ARQ 197-215 study [15]
The survival analysis according to treatment arm suggested that the overall survival (OS) benefit deriving from tivantinib over placebo could be greater in patients with NLR >3, compared to patients with NLR ≤3
Summary
Hepatocellular carcinoma (HCC) accounts for nearly 80% of primary liver cancer cases [1] and it is a leading cause of death worldwide [2]. Among patient-related factors that drive prognosis, mounting evidences suggest that cancer-associated inflammation is a determinant of disease progression and survival in several cancer types, including HCC [4, 5]. The neutrophil-to-lymphocyte ratio (NLR), which is hematological surrogate marker of the systemic inflammatory response, has gained lot of interest in the last decade [6]. In HCC, infiltrating neutrophils may affect disease initiation and progression acting through immunosuppressive mechanisms, which might be mediated either by abnormal chemokine CCL2 production [7] or increased programmed cell death ligand 1 expression [8]. The densities of both tumor-infiltrating T and B lymphocytes were shown to be associated with improved survival and decreased tumour aggressiveness in HCC patients [10]. An elevated NLR might mirror an imbalance favoring the neutrophil pro-tumorigenic functions at the expenses of a decreased anti-tumor immune surveillance of the host
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