Evidence map›Paper›PMID 27579536›Full record

Trial reportOncotarget2016

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, Bruno Daniele, Stefania Salvagni, Jean-Luc Van Laethem, Hans Van Vlierberghe, Jörg Trojan and 10 more

Open access · diamondAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Guideline
  2. Trial
  3. A Phase Ib/II Study of Ramucirumab in Combination with Emibetuzumab in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Trial
  4. Trial
  5. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Application of Tivantinib for Hepatocellular Carcinoma: A Meta-Analysis Study.Evidence-based complementary and alternative medicine : eCAM · 2022
    Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Morphophenotypic Classification of Hepatocellular Carcinoma: the Biliary/Stem Cell Subgroup and Worst Outcome-Implications on Patient Selection.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2021
    Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 15 institutions in 5 countries.

Lorenza RimassaHumanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Giovanni AbbadessaArQule, Burlington, MA, USA.
Nicola PersoneniHumanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Camillo PortaFondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Ivan BorbathCliniques Universitaires Saint-Luc, Brussels, Belgium.
Bruno DanieleG Rummo Hospital, Benevento, Italy.
Stefania SalvagniAzienda Ospedaliera Universitaria Sant'Orsola-Malpighi, Bologna, Italy.
Jean-Luc Van LaethemErasme University Hospital, Brussels, Belgium.
Hans Van VlierbergheGhent University Hospital, Ghent, Belgium.
Jörg TrojanJ W Goethe-University Hospital, Frankfurt, Germany.
Enrico N De ToniKlinikum der Universitaet Muenchen-Grosshadern, Munich, Germany.
Alan WeissVancouver General Hospital, British Columbia Cancer Clinic, Vancouver, Canada.
Steven MilesCedar Sinai, Los Angeles, CA, USA.
Antonio GasbarriniPoliclinico Universitario Agostino Gemelli, Rome, Italy.
Monica LencioniAzienda Ospedaliero-Universitaria di Pisa, Pisa, Italy.
Maria E LamarArQule, Burlington, MA, USA.
Yunxia WangArQule, Burlington, MA, USA.
Dale ShusterDaiichi Sankyo, Edison, NJ, USA.
Brian E SchwartzArQule, Burlington, MA, USA.
Armando SantoroHumanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Arqule (United States) · USHumanitas University · ITAgostino Gemelli University Polyclinic · ITAzienda Ospedaliera G.Rummo · ITAzienda Ospedaliera Universitaria Pisana · ITCedars-Sinai Medical Center · USCliniques Universitaires Saint-Luc · BEDaiichi Sankyo (United States) · USErasmus Hospital · BEGhent University Hospital · BEGoethe University Frankfurt · DELMU Klinikum · DEPoliclinico San Matteo Fondazione · ITPoliclinico S.Orsola-Malpighi · ITVancouver General Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

conclusionsTumor 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.

Indexed as

AdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, HepatocellularFemaleHumansLiver NeoplasmsMaleMiddle AgedProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesSurvival AnalysisARQ 197Biomarkers, TumorProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesAFPHCCHGFMETsorafenib

Identifiers

PMID27579536
PMCPMC5341932
OpenAlexW2517771094

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.