Piñero F, da Fonseca LG. Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups? World J Gastroenterol 2021; 27(24): 3429-3439 [PMID: 34239261 DOI: 10.3748/wjg.v27.i24.3429]
Corresponding Author of This Article
Federico Piñero, MD, MSc, Academic Research, Doctor, Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, Av. Presidente Perón 1500, Pilar, Buenos Aires B1629HJ, Argentina. fpinerof@cas.austral.edu.ar
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Opinion Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Gastroenterol. Jun 28, 2021; 27(24): 3429-3439 Published online Jun 28, 2021. doi: 10.3748/wjg.v27.i24.3429
Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups?
Federico Piñero, Leonardo Gomes da Fonseca
Federico Piñero, Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires B1629HJ, Argentina
Leonardo Gomes da Fonseca, Clinical Oncology, Insituto do Cancer do Estado de São Paulo, University of São Paulo, São Paulo 05403-000, Brazil
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review, drafting, critical revision and editing; they all have approved the final version.
Conflict-of-interest statement: F Piñero has received Advisory Board and speaker honoraria, and he is consultant for RAFFO, BAYER, LKM-Biotoscana and ROCHE; research grants from the Argentinean National Institute of Cancer (INC ID-190), Argentinean National Ministry of Science and Technology Development (PICT 2017, FONCYT) and from the Latin American Liver Research Educational and Awareness Network (LALREAN).
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: Federico Piñero, MD, MSc, Academic Research, Doctor, Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, Av. Presidente Perón 1500, Pilar, Buenos Aires B1629HJ, Argentina. fpinerof@cas.austral.edu.ar
Received: March 17, 2021 Peer-review started: March 17, 2021 First decision: May 1, 2021 Revised: May 6, 2021 Accepted: May 20, 2021 Article in press: May 20, 2021 Published online: June 28, 2021 Processing time: 99 Days and 17.5 Hours
Abstract
Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.
Core Tip: The strict criteria used in clinical trials in advanced hepatocellular carcinoma have led to a scarcity of available data in a considerable proportion of patients in the real-world practice. The daily challenge of treating these underrepresented subgroups can be overcome by future clinical trials addressing special situations, collaborative studies and real-world data.
