Efficacy and Safety of Bevacizumab for the Treatment of Advanced Hepatocellular Carcinoma: A Systematic Review of Phase II Trials
Open Access
- 19 December 2012
- journal article
- review article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (12), e49717
- https://doi.org/10.1371/journal.pone.0049717
Abstract
Hepatocellular carcinoma (HCC) is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. PubMed, the Cochrane Library, and Google Scholar were searched using the terms “bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable)”. Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS), tumor response, and toxicities. A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial) or in combination with erlotinib (n = 4 trials), capecitabine (n = 1 trial), capecitabine+oxaliplatin (n = 1 trial), or gemcitabine+oxaliplatin (n = 1 trial). Most trials (five of eight) reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%), fatigue (12%), hypertension (10%), diarrhea (8%), and neutropenia (5%). Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12), typically due to esophageal varices. Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently approved treatment for unresectable HCC. Phase III trials are warranted to comprehensively examine the efficacy and safety of bevacizumab for treatment of advanced HCC.Keywords
This publication has 29 references indexed in Scilit:
- Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory diseaseInvestigational New Drugs, 2012
- Hepatocellular carcinomaThe Lancet, 2012
- Signaling Pathways in Hepatocellular CarcinomaOncology, 2011
- Asian Consensus Workshop Report: Expert Consensus Guideline for the Management of Intermediate and Advanced Hepatocellular Carcinoma in AsiaOncology, 2011
- Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinomaCancer, 2011
- Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely definedAnnals Of Oncology, 2008
- Sorafenib in Advanced Hepatocellular CarcinomaNew England Journal of Medicine, 2008
- Phase II Trial Evaluating the Clinical and Biologic Effects of Bevacizumab in Unresectable Hepatocellular CarcinomaJournal of Clinical Oncology, 2008
- Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinomaCancer, 2007
- Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic TherapyScience, 2005