Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications

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Abstract

Over the past ten years, sorafenib, a multikinase inhibitor, has been the only systemic agent approved for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Whereas only recently lenvatinib was shown to be noninferior to sorafenib, in terms of survival, all other agents previously tested failed to prove noninferiority (or superiority) when compared with sorafenib. Similarly, in a second-line setting, most investigational drugs have failed to provide better survival outcomes than placebo. However, in 2016, data from the RESORCE trial, a phase 3 study evaluating regorafenib in HCC patients who experience disease progression after first-line treatment with sorafenib, have shown a 2.8-month median survival benefit over placebo (10.6 versus 7.8 months). Overall, side-effects were in line with the known safety profile of regorafenib. More recently, the survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with cabozantinib in the frame of the phase 3 CELESTIAL trial. As HCC seems to be an attractive target for immunotherapy, a phase 1/2 trial reported promising efficacy signals from nivolumab, and results of a larger phase 3 trial with another checkpoint inhibitor, namely, pembrolizumab, are still pending. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and immunotherapy that will likely change the treatment scenario of HCC.

Keywords: advanced, angiogenesis, hepatocellular carcinoma, immunotherapy, metastatic, multikinase inhibition, regorafenib, second-line.

Citation: Personeni N, Pressiani T, Santoro A, Rimassa L. Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications. Drugs in Context 2018; 7: 212533. DOI: 10.7573/dic.212533

Contributions: All authors performed the research, writing, and review of all drafts of this manuscript and approved the final draft.

Disclosure and potential conflicts of interest: Dr Rimassa reports personal fees from Bayer, personal fees and non-financial support from Arqule, personal fees from Lilly, personal fees from Sirtex medical, personal fees from Exelixis, personal fees and non-financial support from Ipsen, personal fees from AstraZeneca, but not connected with the submitted work. Dr Santoro declares support from Bayer, Takeda Lilly, Amgen, Arqule, Bristol-Myers Squibb, Cegene, Merck Sharp and Dohme, Novartis, Roche, Servier, Eisai, but not connected with the submitted work. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at https://www.drugsincontext.com/wp-content/uploads/2018/06/dic.212533-COI.pdf

Funding declaration: No funds were provided for this review nor for medical writing assistance.

Copyright: Copyright © 2018 Personeni N, Pressiani T, Santoro A, Rimassa L. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2018 Personeni N, Pressiani T, Santoro A, Rimassa L. https://doi.org/10.7573/dic.212533. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/regorafenib-in-hepatocellular-carcinoma-latest-evidence-and-clinical-implications

Correspondence: Lorenza Rimassa, Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy lorenza.rimassa@cancercenter.humanitas.it

Provenance: invited; externally peer reviewed.

Submitted: 5 April 2018; Peer review comments to author: 11 May 2018; Revised manuscript received: 25 May 2018; Accepted: 1 June 2018; Publication date: 27 June 2018.

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