LBA-03 Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial

Bruix, Jordi; Merle, Philippe; Granito, Alessandro; Huang, Yi Hsiang; Bodoky, G.; Yokosuka, Osamu; Rosmorduc, Olivier; Breder, Valeriy Vladimirovich; Gerolami, René; Masi, Gianluca; Paul, J. Ross; Qin, Shukui; Song, Tianqiang; Bronowicki, Jean Pierre; Ollivier-Hourmand, Isabelle; Kudo, Masatoshi; LeBerre, M.-A.; Baumhauer, Annette; Meinhardt, Gerold; Han, Guo Hong

doi:10.1093/annonc/mdw237.03

Cited by 44 publications

(36 citation statements)

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“…Biological selection of patients remains crucial for the development of targeted therapies in this population, as demonstrated by the general lack of success of phase III studies with unselected HCC patients, except for the recent regorafenib study [45]. Only recently the REACH study, although negative in the overall population, identified AFP as a possible biomarker for patient selection for treatment with ramucirumab [38].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…At the European Society of Medical Oncology World Congress of Gastrointestinal Cancer held in Barcelona, Spain, on 30 th June 2016, positive outcomes were reported by the Study of Regorafenib after Sorafenib in Patients with Hepatocellular Carcinoma (RESORCE) trial, which investigated the efficacy of regorafenib as second-line therapy after sorafenib failure [1]. In this clinical trial, the group who received regorafenib achieved a survival benefit of approximately 2.8 months compared to the placebo group.…”

Section: Introductionmentioning

confidence: 99%

Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma

2016

Liver Cancer

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“…Many novel therapies are currently under investigation in clinical trials. In a recently published Phase III trial, regorafenib, an oral multikinase inhibitor, has demonstrated an increase in median overall survival (10.6 months vs. 7.8 months) and an increase in median progression-free survival (PFS; 3.1 months vs. 1.5 months) compared to placebo in patients with advanced HCC who have progressed on sorafenib 12. To date, however, there are no FDA-approved second-line or salvage therapies for those patients who progress with or are intolerant to sorafenib 13…”

Section: Introductionmentioning

confidence: 99%

Profile of tivantinib and its potential in the treatment of hepatocellular carcinoma: the evidence to date

Pievsky¹,

Pyrsopoulos

2016

JHC

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Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States and carries a very poor prognosis, with a median survival time of <50% at 1 year for advanced disease. To date, sorafenib is the only therapy approved by the Food and Drug Administration for the treatment of advanced HCC. Tivantinib (ARQ-197), a non-ATP competitive inhibitor of cellular mesenchymal–epithelial transcription factor (c-MET), has shown a survival benefit in patients with advanced HCC who have failed or are intolerant to sorafenib in Phase I and II trials. Those patients who have tumors with high concentrations of MET (MET-high) appear to derive the greatest benefit from tivantinib therapy. Currently, two large randomized double-blind placebo-controlled Phase III trials (METIV-HCC [NCT01755767] and JET-HCC [NCT02029157]) are evaluating tivantinib in patients with MET-high advanced HCC, with the primary end points of overall survival and progression-free survival, respectively. This study reviews the evidence for the use of tivantinib in advanced HCC. Specific topics addressed include the pharmacology, dosing, toxicity, and biomarkers associated with tivantinib use.

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LBA-03 Efficacy and safety of regorafenib versus placebo in patients with hepatocellular carcinoma (HCC) progressing on sorafenib: results of the international, randomized phase 3 RESORCE trial

Cited by 44 publications

References 0 publications

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

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

Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma

Profile of tivantinib and its potential in the treatment of hepatocellular carcinoma: the evidence to date

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