G06 : A randomized, double-blind, placebo-controlled phase III trial of TSU-68 (orantinib) combined with transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma

Park, J.-W.; Cheng, A-L.; Kudo, Masatoshi; Park, J.H.; Liang, Po-Chin; Hidaka, Hiroyoshi; Izumi, Namiki; Heo, Jeong; Lee, Y.J.; Is, Sheen; Chiu, Chang‐Fang; Arioka, Hitoshi; Morita, Satoshi; Arai, Young‐Chang P.

doi:10.1016/s0168-8278(15)30007-6

Cited by 7 publications

(4 citation statements)

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“…This oral kinase inhibitor targets VEGFR2, PDGFR, and FGFR to suppress angiogenesis [25] . A phase III trial comparing orantinib and placebo in combination therapy with TACE (ORIENTAL study) was ter-minated after the interim analysis because the criteria for trial continuation regarding the primary endpoint of OS were not met [26] . The failure of this trial could be attributed to the considerable toxicity of orantinib.…”

Section: Current Status Of the Development Of Molecular Targeted Agenmentioning

confidence: 99%

Systemic Therapy for Hepatocellular Carcinoma: 2017 Update

Kudo

2017

Oncology

107

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Systemic therapy for hepatocellular carcinoma (HCC) changed drastically after the introduction of the molecular targeted agent sorafenib in 2007. Sorafenib provides an additional therapeutic option for patients with extrahepatic spread or vascular invasion, resulting in improved survival even among patients with advanced HCC; however, the toxicity of sorafenib and its unsatisfactory antitumor effects remain unsolved issues. The development of novel molecular targeted agents as alternatives to sorafenib has been limited by difficulties unique to HCC. Recent studies have demonstrated the efficacy of two molecular targeted agents, the second-line agent regorafenib, which is used after sorafenib failure, and the first-line agent lenvatinib, which has been shown to be noninferior to sorafenib. Another category of agents that are attracting considerable interest are immune checkpoint inhibitors such as anti-PD-1/PD-L1 or CTLA-4 antibodies, which kill cancer cells via a unique mechanism. The therapeutic effects of some of these agents are currently under investigation in phase III studies. The most recent topics of interest are the combination of anti-PD-1/PD-L1 therapies with other immune checkpoint inhibitors, such as anti-CTLA-4 antibodies, or with a tyrosine kinase inhibitor, or with locoregional therapies such as resection, ablation, or transarterial chemoembolization.

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Section: Current Status Of the Development Of Molecular Targeted Agenmentioning

confidence: 99%

Systemic Therapy for Hepatocellular Carcinoma: 2017 Update

Kudo

2017

Oncology

107

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“…The Transcatheter Arterial Chemoembolization Therapy in Combination with Sorafenib (TACTICS) study conducted in Japan is the only large-scale clinical trial that is currently underway. As shown in Table 1, negative outcomes have also been reported in studies with other agents, including the Brivanib versus Placebo as Adjuvant Therapy to Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma (BRISK-TA) study [8], a phase III study on brivanib (an inhibitor of vascular endothelial growth factor receptor [VEGFR] and fibroblast growth factor receptor [FGFR]), and the Orantinib in Combination with Transcatheter Arterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma (ORIENTAL) study, a phase III study on orantinib (an inhibitor of VEGFR, platelet-derived growth factor receptor [PDGFR], and FGFR [9]).…”

Section: Current Status Of the Development Of Molecular Targeted Agentsmentioning

confidence: 99%

Molecular Targeted Agents for Hepatocellular Carcinoma: Current Status and Future Perspectives

Kudo¹

2016

Liver Cancer

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“…In combination with transarterial chemoembolization (TACE), a phase III study was conducted but was terminated after interim analysis did not reach the primary outcome of OS. The final analysis of 889 patients showed median OS of 31 months after TACE with TSU-68 and 32.3 months after TACE with placebo but the median time to TACE failure was longer in the TSU-68 arm with 23.9 months vs. 19.8 months for the placebo arm [ 84 ].…”

Section: Molecularly Targeted Agentmentioning

confidence: 99%

Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

2015

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.

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G06 : A randomized, double-blind, placebo-controlled phase III trial of TSU-68 (orantinib) combined with transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma

Cited by 7 publications

References 0 publications

Systemic Therapy for Hepatocellular Carcinoma: 2017 Update

Systemic Therapy for Hepatocellular Carcinoma: 2017 Update

Molecular Targeted Agents for Hepatocellular Carcinoma: Current Status and Future Perspectives

Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

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