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Ramucirumab, A Second-Line Option For Patients With Hepatocellular Carcinoma: A Review Of The Evidence

Authors De Luca E, Marino D, Di Maio M

Received 8 January 2020

Accepted for publication 27 April 2020

Published 20 May 2020 Volume 2020:12 Pages 3721—3729

DOI https://doi.org/10.2147/CMAR.S216220

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Emmanuele De Luca,1,2,* Donatella Marino,1,2,* Massimo Di Maio1,2

1Department of Oncology, University of Turin, Torino, Italy; 2Division of Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy

*These authors contributed equally to this work

Correspondence: Massimo Di Maio
Division of Medical Oncology, Ordine Mauriziano Hospital, Via Magellano 1, Turin 10128, Italy
Tel +39 011 5082032
Fax +39 011 5085081
Email massimo.dimaio@unito.it

Abstract: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and predominantly develops in patients with liver cirrhosis. In patients with advanced disease, such as extra-hepatic extension or portal vein involvement, and with intermediate disease unsuitable for locoregional therapies, systemic therapy is recommended, if liver function and performance status are adequate. Following a decade of negative Phase III trials since the approval of sorafenib, more recently several drugs have proven efficacy both in first line versus sorafenib (lenvatinib) or in second line versus placebo (regorafenib, cabozantinib, ramucirumab). In this review, we summarize the preclinical and clinical evidence supporting the use of ramucirumab, a recombinant IgG1 monoclonal antibody that specifically binds to Vascular Endothelial Growth Factor receptor 2 (VEGFR-2), in HCC. Following the results of the REACH trial, that was negative in the overall study population but identified a subgroup that could benefit from ramucirumab treatment, the REACH-2 trial was a randomized, placebo-controlled trial, designed to assess ramucirumab as second line in patients with alpha-fetoprotein (AFP) ≥ 400 ng/mL. The results of REACH-2 were published in February 2019, leading to Food and Drug Administration and European Medicines Agency approval of the drug as second-line agent for advanced HCC (after sorafenib) in patients with AFP ≥ 400 ng/mL. For the first time in the history of systemic treatments for HCC, a predictive factor of efficacy was identified. In this review, we also discuss the potential clinical development of systemic treatments in HCC, focusing on combination therapies with immunotherapy (following the recent results of the combination of atezolizumab and bevacizumab in the IMbrave 150 clinical trial) and treatment sequences as a way to maximize survival benefit.

Keywords: ramucirumab, hepatocellular carcinoma, VEGF, immunotherapy

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