Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1813-1832
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1813
Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review
Faiza Ahmed, Jennifer Onwumeh-Okwundu, Zeynep Yukselen, Maria-Kassandra Endaya Coronel, Madiha Zaidi, Prathima Guntipalli, Vamsi Garimella, Sravya Gudapati, Marc Darlene Mezidor, Kim Andrews, Mohamad Mouchli, Endrit Shahini
Faiza Ahmed, Zeynep Yukselen, Maria-Kassandra Endaya Coronel, Madiha Zaidi, Prathima Guntipalli, Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, FL 33143, United States
Jennifer Onwumeh-Okwundu, Community Health Division, University of Stellenbosch, Stellenbosch 7602, South Africa
Vamsi Garimella, College of Medicine, Howard University, Washington, DC 520, United States
Sravya Gudapati, College of Medicine, Washington University of Health and Science, San Pedro, Belize
Marc Darlene Mezidor, Department of Radiology, Amita Health Saint Francis Hospital, Evaston, IL 60202, United States
Kim Andrews, Department of Mathematics and Natural Sciences, Prince Mohammad Bin Fahad University, Al Khobar 31952, Saudi Arabia
Mohamad Mouchli, Department of Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, United States
Endrit Shahini, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte (Bari) 70013, Italy
Author contributions: Ahmed F, Onwumeh-Okwundu J, and Shahini E were the guarantors of the study; Ahmed F and Onwumeh-Okwundu J contributed to the study conception, design, and data acquisition, and supervised the drafting of the manuscript; Ahmed F, Mouchli M, and Shahini E critically reviewed the manuscript; Ahmed F, Endaya Coronel MK, Mouchli M, and Shahini E assisted in formatting, editing and revising the manuscript; All authors interpreted the data, participated in drafting the manuscript, critically revised the article for important intellectual content, and gave final approval of the article to be published.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Endrit Shahini, MD, MSc, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte (Bari), Via Turi 27, Castellana Grotte (Bari) 70013, Italy. endrit.shahini@irccsdebellis.it
Received: March 12, 2021
Peer-review started: March 12, 2021
First decision: May 3, 2021
Revised: May 11, 2021
Accepted: August 25, 2021
Article in press: August 25, 2021
Published online: November 15, 2021
Processing time: 245 Days and 11.2 Hours
Abstract
BACKGROUND

Despite the use of current standard therapy, the prognosis of patients with unresectable hepatocellular carcinoma (HCC) is poor, with median survival times of 40 mo for intermediate HCC (Barcelona Clinic Liver Cancer [BCLC] stage B) and 6–8 mo for advanced HCC (BCLC stage C). Although patients with early-stage HCC are usually suitable for therapies with curative intention, up to 70% of patients experience relapse within 5 years. In the past decade, the United States Food and Drug Administration has approved different immunogenic treatment options for advanced HCC, the most common type of liver cancer among adults. Nevertheless, no treatment is useful in the adjuvant setting. Since 2007, the multi-kinase inhibitor sorafenib has been used as a first-line targeted drug to address the increased mortality and incidence rates of HCC. However, in 2020, the IMbrave150 trial demonstrated that combination therapy of atezolizumab (anti-programmed death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [VEGF]) is superior to sorafenib, a single anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer monotherapy for HCC treatment.

AIM

To conduct a systematic literature review to evaluate the evidence supporting the efficacy and safety of atezolizumab/bevacizumab as preferred first-line drug therapy over the conventional sorafenib or atezolizumab monotherapies, which are used to improve survival outcomes and reduce disease progression in patients with unresectable HCC and non-decompensated liver disease.

METHODS

A comprehensive literature review was conducted using the PubMed, Scopus, ScienceDirect, clinicaltrials.gov, PubMed Central, Embase, EuropePMC, and CINAHL databases to identify studies that met the inclusion criteria using relevant MeSH terms. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias (RoB) were assessed using the Cochrane RoB 2 tool and Sevis.

RESULTS

In the atezolizumab/bevacizumab group, an improvement in overall tumor response, reduction of disease progression, and longer progression-free survival were observed compared to monotherapy with either sorafenib or atezolizumab. Hypertension and proteinuria were the most common adverse events, and the rates of adverse events were comparable to those with the monotherapy. Of the studies, there were two completed trials and two ongoing trials analyzed using high quality and low bias. A more thorough analysis was only performed on the completed trials.

CONCLUSION

Treatment of HCC with atezolizumab/bevacizumab combination therapy was confirmed to be an effective first-line treatment to improve survival in patients with unresectable HCC and non-decompensated liver disease compared to monotherapy with either sorafenib or atezolizumab.

Keywords: Hepatic malignancy; Combination systemic therapy; Immunogenetic therapy; Liver transplantation; Barcelona clinic liver cancer; Transarterial chemoembolization

Core Tip: Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is a leading cause of cancer-related deaths. Combination immunotherapy for the treatment of advanced HCC is attracting increasing attention because of the superiority of clinical results compared to sorafenib, the standard of care. Combination therapy with atezolizumab/bevacizumab has been compared to sorafenib and atezolizumab monotherapies. Current findings indicate that combination therapy is as effective as first-line therapeutic options for improving survival rates in patients with unresectable HCC and non-decompensated liver disease.