Sorafenib in advanced hepatocellular carcinoma

2008

none 25 BACKGROUND: No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. METHODS: In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Seconda…

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial.

2012

BACKGROUND & AIMS: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety o…

Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma

2014

Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference

2020

Proper trial design is critical for the success of clinical investigations. Hepatocellular carcinoma (HCC) is a complex disease that has several unique properties. In 2008, after the approval of sorafenib, a panel of experts proposed guidelines for trial design and endpoints in HCC that have been instrumental during the last decade and provided a framework to allow an homogeneous analysis of reported investigations. Since then, several phase III studies have been reported and novel challenges have emerged. A panel of experts conveyed by AASLD organized a Special Topic Conference on trial design and endpoints to address those emerging challenges. This review summarizes the analysis and concl…

Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology.

2021

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. METHODS Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche CO…

EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

2018

Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Hepatocellular carcinoma represents about 90% of primary liver cancers and constitutes a major global health problem. The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2.

2020

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods …

Biology and significance of alpha‐fetoprotein in hepatocellular carcinoma

2019

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths globally due, in part, to the majority of patients being diagnosed with intermediate or advanced stage disease. Our increased understanding of the heterogeneous molecular pathogenesis of HCC has led to significant developments in novel targeted therapies. Despite these advances, there remains a high unmet need for new treatment options. HCC is a complex disease with multiple pathogenic mechanisms caused by a variety of risk factors, making it difficult to characterize with a single biomarker. In fact, numerous biomarkers have been studied in HCC, but alpha-fetoprotein (AFP) remains the most widely used …

Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

2020

Abstract Background & Aims Radiological progression patterns to first‐line sorafenib have been associated with post‐progression and overall survival in advanced hepatocellular carcinoma, but these associations remain unknown for therapies in second‐ and later‐line settings. This post hoc analysis of REACH and REACH‐2 examined outcomes by radiological progression patterns in the second‐line setting of patients with advanced hepatocellular carcinoma treated with ramucirumab or placebo. Methods Patients with advanced hepatocellular carcinoma, Child‐Pugh A and Eastern Cooperative Oncology Group Performance Status 0 or 1 with prior sorafenib were randomized to receive ramucirumab 8mg/kg or place…