Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

Lorenza Rimassa, Giovanni Abbadessa, Nicola Personeni, Camillo Porta, Ivan Borbath, B. Daniele, Stefania Salvagni, Jean Luc Van Laethem, H. Van Vlierberghe, J. Trojan, Enrico de Toni, Alan Weiss, Steven Miles, A. Gasbarrini, Monica Lencioni, M. Lamar, Yunxia Wang, Dale Shuster, Brian Schwartz, Armando Santoro

Research output: Contribution to journalArticle

Abstract

ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials.

Original languageEnglish
Pages (from-to)72622-72633
Number of pages12
JournalOncotarget
Volume7
Issue number45
DOIs
Publication statusPublished - 2016

Fingerprint

Tumor Biomarkers
Hepatocellular Carcinoma
Hepatocyte Growth Factor
Biomarkers
Neoplasms
alpha-Fetoproteins
Vascular Endothelial Growth Factor A
Survival
Proto-Oncogene Proteins c-met
Methylnitronitrosoguanidine
Oncogenes
ARQ 197
Randomized Controlled Trials
Immunohistochemistry
Placebos
Serum
Research

Keywords

  • AFP
  • HCC
  • HGF
  • MET
  • Sorafenib

ASJC Scopus subject areas

  • Oncology

Cite this

Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib. / Rimassa, Lorenza; Abbadessa, Giovanni; Personeni, Nicola; Porta, Camillo; Borbath, Ivan; Daniele, B.; Salvagni, Stefania; Van Laethem, Jean Luc; Van Vlierberghe, H.; Trojan, J.; de Toni, Enrico; Weiss, Alan; Miles, Steven; Gasbarrini, A.; Lencioni, Monica; Lamar, M.; Wang, Yunxia; Shuster, Dale; Schwartz, Brian; Santoro, Armando.

In: Oncotarget, Vol. 7, No. 45, 2016, p. 72622-72633.

Research output: Contribution to journalArticle

Rimassa, L, Abbadessa, G, Personeni, N, Porta, C, Borbath, I, Daniele, B, Salvagni, S, Van Laethem, JL, Van Vlierberghe, H, Trojan, J, de Toni, E, Weiss, A, Miles, S, Gasbarrini, A, Lencioni, M, Lamar, M, Wang, Y, Shuster, D, Schwartz, B & Santoro, A 2016, 'Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib', Oncotarget, vol. 7, no. 45, pp. 72622-72633. https://doi.org/10.18632/oncotarget.11621
Rimassa, Lorenza ; Abbadessa, Giovanni ; Personeni, Nicola ; Porta, Camillo ; Borbath, Ivan ; Daniele, B. ; Salvagni, Stefania ; Van Laethem, Jean Luc ; Van Vlierberghe, H. ; Trojan, J. ; de Toni, Enrico ; Weiss, Alan ; Miles, Steven ; Gasbarrini, A. ; Lencioni, Monica ; Lamar, M. ; Wang, Yunxia ; Shuster, Dale ; Schwartz, Brian ; Santoro, Armando. / Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib. In: Oncotarget. 2016 ; Vol. 7, No. 45. pp. 72622-72633.
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abstract = "ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82{\%}) versus before (40{\%}) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials.",
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AU - Rimassa, Lorenza

AU - Abbadessa, Giovanni

AU - Personeni, Nicola

AU - Porta, Camillo

AU - Borbath, Ivan

AU - Daniele, B.

AU - Salvagni, Stefania

AU - Van Laethem, Jean Luc

AU - Van Vlierberghe, H.

AU - Trojan, J.

AU - de Toni, Enrico

AU - Weiss, Alan

AU - Miles, Steven

AU - Gasbarrini, A.

AU - Lencioni, Monica

AU - Lamar, M.

AU - Wang, Yunxia

AU - Shuster, Dale

AU - Schwartz, Brian

AU - Santoro, Armando

PY - 2016

Y1 - 2016

N2 - ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials.

AB - ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials.

KW - AFP

KW - HCC

KW - HGF

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