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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

41 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)72622-72633
Numero di pagine12
RivistaOncotarget
Volume7
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • AFP
  • HCC
  • HGF
  • MET
  • Oncology
  • Sorafenib

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