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Published online: 7 February 2020
© Springer Nature Switzerland AG 2020
Abstract
Ramucirumab ( Cyramza®), a fully human anti-VEGFR-2 monoclonal antibody, has been approved as monotherapy for the treatment of patients with hepatocellular carcinoma (HCC) and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib. Ramucirumab significantly prolonged overall survival (OS) and progression-free survival (PFS) relative to placebo in this population in the randomized, double-blind phase 3 REACH 2 trial. These benefits were seen in key prespecified subgroups based on demographic and disease characteristics. Ramucirumab had an acceptable tolerability profile and manageable safety profile in these patients, with the majority of treatment-related adverse events being mild or moderate in severity. The safety profile of ramucirumab was consistent with that expected for agents targeting the VEGF/VEGFR axis. Currently, ramucirumab is the only therapy specifically tested in patients with α-fetoprotein levels ≥ 400 ng/mL, which is associated with an aggressive disease and poor prognosis. Therefore, ramucirumab is an important treatment option for patients with HCC and α-fetoprotein levels ≥ 400 ng/mL who have been treated with sorafenib.
1Introduction
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a leading cause of cancer-related death worldwide [1]. Liver diseases involving cirrhosis of any aetiology increase the risk of HCC; thus, hepatitis B or C virus infection, alcohol abuse and non-alcoholic fatty liver disease are the most common risk factors for HCC [2]. The risk of HCC varies based on aetiology, extent of liver damage, sex, age and geographical area [2]. Serum a-fetoprotein level has a prognostic value in patients with HCC, with elevated levels (typically > 400 ng/mL) associated with poor prognosis [3].
HCC is asymptomatic for most of its natural course and is typically diagnosed only at an advanced stage in many patients [4]. The modified Barcelona Clinic Liver Cancer (BCLC) staging system defines intermediate HCC (stage B) as preserved liver function, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 and multinodular unresectable tumours, and defines advanced HCC (stage C) as preserved liver function, and either ECOG PS score of 1-2, macrovascular invasion or extrahepatic spread [5]. Without treatment, the expected median overall survival (OS) in patients with advanced HCC is 6-8 months [5].
Treatment options for HCC are...