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

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

doi:10.18632/oncotarget.14797

Cited by 27 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the writing of this manuscript, exploratory analyses from two prospective studies performed in patients with advanced HCC have been published: Personeni et al analysed the prognostic value of NLR in patients treated in the ARQ 197–215 study, a randomised placebo-controlled study testing the MET inhibitor tivantinib in the second line setting for patients with advanced HCC [ 30 ]. Multivariate analysis revealed that baseline NLR was an independent prognostic biomarker in this setting; NLR >3 was associated with poorer survival (HR1.65; 95% CI 1.05; 2.59; p = 0.03) [ 30 ]. Bruix et al conducted a pooled exploratory analysis from the 2 landmark placebo-controlled phase 3 studies (SHARP and Asia-Pacific) in an attempt to identify prognostic factors for OS and predictive factors of sorafenib benefit [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Non-secretion of AFP and neutrophil lymphocyte ratio as predictors for survival in hepatocellular carcinoma patients treated with sorafenib: a large UK cohort

et al. 2018

View full text Add to dashboard Cite

BackgroundSorafenib is the current standard of care for patients with advanced or metastatic hepatocellular carcinoma. Currently no universally agreed model exists correlating the Neutrophil Lymphocyte ratio (NLR) and non-secretion of AFP with the survival of HCC patients treated with sorafenib.Patients and MethodsWe retrospectively analysed patient records with a confirmed diagnosis of HCC treated with sorafenib between April 2009 and March 2014. Survival analysis was performed using the Kaplan–Meier method and Cox regression.ResultsPatients separated into groups based on NLR (≤3 or >3), or AFP secretion profile (<7 ng/ml or ≥7 ng/ml) derived diverging Kaplan–Meier curves for overall survival (OS). The median OS in those with NLR ≤3.0 was 9.0 months (95% CI: 7.7–11.1 months) and in those with NLR >3.0 it was 6.0 months (95% CI: 4.9–8.2 months) [HR 1.32 (95% CI: 0.96–1.80)]. The median overall survival post sorafenib was higher in the “non-secretor” AFP group. OS for AFP <7 ng/ml was 10.0 months (95% CI: 7.7–19.3 months) compared to AFP ≥7ng/ml: 6.6 months (95% CI: 5.3–8.4 months) [HR 1.64 (95% CI: 1.15–2.33)].ConclusionNLR and AFP non - secretion at diagnosis are potential significant prognosticators for overall survival from initiation of sorafenib.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-secretion of AFP and neutrophil lymphocyte ratio as predictors for survival in hepatocellular carcinoma patients treated with sorafenib: a large UK cohort

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In this study the authors observed that a baseline high NLR (greater than 3) is an independent prognostic biomarker in patients with HCC who are candidate for second-line treatments. An important finding was that for overall survival, no interaction was detected between NLR status and treatment [ 36 ]. These results confirm that NLR have a prognostic value regardless the treatment applied.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib

et al. 2017

View full text Add to dashboard Cite

Neutrophil-to-lymphocyte ratio (NLR) is considered a prognostic factor in patients with hepatocellular carcinoma (HCC). Our aim is to investigate the prognostic significance of NLR in patients with HCC treated with sorafenib.ResultsMedian follow-up time was 7 months. Patients were mostly in the intermediate (27.3%) or advanced (72.7%) BCLC stages, 38.6% had vascular invasion and 27.5% extrahepatic disease. A large proportion (38.9%) had been previously treated with TACE. Liver function was preserved: 65.8% were classed as Child A. Median overall survival was 7.7 months (95% CI: 5.8–9.6). In univariate analysis, vascular invasion (P = 0.004), ECOG-PS ≥ 1 (P < 0.001), high bilirubin (P < 0.001), clinical ascites (P = 0.036), BCLC stage (P = 0.004), no previous TACE (P = 0.041) and NRL ≥ 2.3 (P = 0.005) were predictors of poor survival. Skin toxicity (P = 0.039) or hypertension (P = 0.033) during treatment were related to better survival. In multivariate analysis NLR ≥ 2.3 [HR 1.72 (95% CI: 1.03–2.71)], hyperbilirubinemia [HR 3.42 (95% CI: 1.87–6.25)] and ECOG-PS ≥ 1 [HR 1.97 (95% CI: 1.19–3.26)] were found as independent indicators of poor overall survival. Dermatologic adverse effects were an indicator of good overall survival [HR 0.59 (95% CI: 0.38–0.92)].Material and MethodsOne hundred and fifty-four consecutive HCC patients treated with sorafenib in four different Spanish hospitals between August 2005 and October 2013 were analysed. Clinical, laboratory, and tumour features were obtained. Survival was calculated from the moment sorafenib treatment was initiated. Log-rank and Cox regression were used to analyse the ability of NLR to predict survival.ConclusionsNLR is an independent prognostic indicator for overall survival in HCC patients treated with sorafenib.

show abstract

“…Initial tumor biomarker analysis from this study showed the prognostic value and the predictive value of MET expression as a marker of benefit from tivantinib [ 25 ]. Further biomarker analyses from the same study suggested that tumor MET levels were higher in patients previously treated with sorafenib, circulating biomarkers such as MET and HGF might be prognostic in second-line HCC [ 26 ], and baseline neutrophil-to-lymphocyte ratio was an independent prognostic biomarker [ 27 ]. Based on the phase 2 results, tivantinib has been evaluated in two phase 3 trials in previously treated patients with high tumor MET expression, the METIV-HCC trial in western countries [ 21 ], and the JET-HCC trial in Japan [ 22 ].…”

Section: Negative Studies For Second-line Treatment Of Hccmentioning

confidence: 99%

Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications

Personeni

Pressiani

Santoro

et al. 2018

DIC

Self Cite

View full text Add to dashboard Cite

Over the past ten years, sorafenib, a multikinase inhibitor, has been the only systemic agent approved for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Whereas only recently lenvatinib was shown to be noninferior to sorafenib, in terms of survival, all other agents previously tested failed to prove noninferiority (or superiority) when compared with sorafenib. Similarly, in a second-line setting, most investigational drugs have failed to provide better survival outcomes than placebo. However, in 2016, data from the RESORCE trial, a phase 3 study evaluating regorafenib in HCC patients who experience disease progression after first-line treatment with sorafenib, have shown a 2.8-month median survival benefit over placebo (10.6 versus 7.8 months). Overall, side-effects were in line with the known safety profile of regorafenib. More recently, the survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with cabozantinib in the frame of the phase 3 CELESTIAL trial. As HCC seems to be an attractive target for immunotherapy, a phase 1/2 trial reported promising efficacy signals from nivolumab, and results of a larger phase 3 trial with another checkpoint inhibitor, namely, pembrolizumab, are still pending. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and immunotherapy that will likely change the treatment scenario of HCC.

show abstract

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

Cited by 27 publications

References 25 publications

Non-secretion of AFP and neutrophil lymphocyte ratio as predictors for survival in hepatocellular carcinoma patients treated with sorafenib: a large UK cohort

Non-secretion of AFP and neutrophil lymphocyte ratio as predictors for survival in hepatocellular carcinoma patients treated with sorafenib: a large UK cohort

Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib

Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications

Contact Info

Product

Resources

About