Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial

Meyer, Tim; Fox, Richard; Ting, Yuk; Ross, Paul; James, Martin; Sturgess, Richard; Stubbs, Clive; Stocken, Deborah; Wall, Lucy; Watkinson, Anthony; Hacking, Nigel; Evans, T.R. Jeffry; Collins, Peter L.; Hubner, Richard A; Cunningham, David; Primrose, John; Johnson, Philip J.; Palmer, Daniel H.

doi:10.1016/s2468-1253(17)30156-5

Cited by 399 publications

(358 citation statements)

References 30 publications

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“…In addition, the ORR of lenvatinib is similar to the world standard ORR of TACE therapy (Fig. 2) [11][12][13], indicating that it could replace TACE in certain populations of intermediate-stage HCC patients in the very near future.…”

Section: Association Between Response To Molecular Targeted Agents Anmentioning

confidence: 55%

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Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma

Kudo

2018

Liver Cancer

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Section: Association Between Response To Molecular Targeted Agents Anmentioning

confidence: 55%

“…( Fig. 2, 3) than the ORR by world standard of TACE, which was 42% in the placebo arm from the BRISK-TA trial or two other trials [11][12][13], and much higher than the ORR of 52% for the first TACE session in real-world practice in Japan according to the OPTIMIS study (Fig. 4) [14][15][16].…”

Section: Orr Of Lenvatinib In the Japanese Subpopulation From The Refmentioning

confidence: 99%

Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma

Kudo

2018

Liver Cancer

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“…Background Twenty institutes in England participated in this study, which aimed to clarify whether combination therapy with DEB-TACE and sorafenib suppresses tumor progression and extends OS [16] .…”

Section: The Tace-2 Studymentioning

confidence: 99%

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2)

Kudo

Arizumi²

2017

Oncology

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sessment Randomized Protocol (SHARP) and Asia-Pacific studies [1,2] . In 2007, sorafenib was approved in the EU and USA, where it became a first-line agent for unresectable advanced HCC. Transarterial chemoembolization (TACE) is the first-line treatment option for intermediate-stage HCC [3][4][5][6] ; however, repeated TACE sessions tend to impair liver functional reserve. Reducing the frequency of TACE, which is generally repeated upon tumor progression, is a challenging issue in the treatment of patients with intermediate-stage HCC. To address this issue, previous trials combined molecular targeted agents with TACE; however, the safety and efficacy of this combination could not be demonstrated, and none of the combination therapies is currently recommended.In the SHARP study, subanalysis showed that the hazard ratio (HR) for overall survival (OS) in patients with HCC with no vascular invasion or extrahepatic spread, which are regarded as good indications for TACE, was 0.52 and, thus, extremely good in the sorafenib group. The median survival of these patients was extended approximately 1.5-fold [7] , suggesting that the addition of sorafenib as adjuvant therapy to TACE improves prognosis. The combination of TACE with sorafenib does not simply represent the administration of 2 types of treatment; the combination is expected to extend the period during which TACE controls tumor progression because sorafenib strongly suppresses post-TACE tumor recur- AbstractThe multikinase inhibitor sorafenib is the first oral molecular targeted agent with proven prognostic benefit in unresectable advanced hepatocellular carcinoma (HCC). However, as with other drugs, sorafenib has its limitations, and various clinical trials have been conducted to develop novel molecular targeted agents for use alone or in combination with existing locoregional therapies. Despite this, clinical trials of molecular targeted agents combined with transarterial chemoembolization (TACE) have not reported major treatment outcomes to date. In this review, we describe previous clinical trials of combination therapy with TACE and a molecular targeted agent in patients with unresectable HCC.

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“…Another disadvantage of TACE is that repeated procedures reduce liver function [6]; therefore, minimizing the number of TACE sessions is a critical challenge in the treatment of intermediate-stage HCC patients. Several clinical trials have attempted to address this problem by combining TACE with molecular targeted agents; however, to date, all have ended in failure [7-11], and the combination of TACE and molecular targeted agents is therefore not recommended in routine practice.…”

Section: Introductionmentioning

confidence: 99%

Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

Kudo¹

2018

Liver Cancer

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Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial

Abstract: Bayer PLC and BTG PLC.

Cited by 399 publications

References 30 publications

Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma

Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2)

Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

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