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World J Hepatol. Jun 27, 2022; 14(6): 1074-1086
Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1074
Second-line treatment of advanced hepatocellular carcinoma: Time for more individualized treatment options?
Senthil Rajappa, Kun-Ming Rau, Palanki Satya Dattatreya, Anant Ramaswamy, Philana Fernandes, Aarohan Pruthi, Rebecca Cheng, Mariusz Lukanowski, Yi-Hsiang Huang
Senthil Rajappa, Department of Medical Oncology, Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad 500034, Telangana, India
Kun-Ming Rau, College of Medicine, I-Shou University, Kaohsiung 822, Taiwan
Palanki Satya Dattatreya, Department of Oncology, Omega Hospital, Hyderabad 500034, India
Anant Ramaswamy, Department of Oncology, Tata Memorial Hospital, Mumbai 400012, India
Philana Fernandes, Global Scientific Communications, Eli Lilly and Company Ltd, Cork 48006, Cork, Ireland
Aarohan Pruthi, Medical Affairs, Eli Lilly India, Haryana 122001, India
Rebecca Cheng, Medical Affairs, Eli Lilly Taiwan, Taipei 10543, Taiwan
Mariusz Lukanowski, Medical Affairs, Eli Lilly, Herlev 2370, Denmark
Yi-Hsiang Huang, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming Yang Ming Chiao Tung University School of Medicine, Taipei 112, Taiwan
Author contributions: Pruthi A, Cheng R, and Lukanowski M contributed to the study design; and all authors were involved in the data analysis and interpretation, drafting, review, and approval of the review.
Conflict-of-interest statement: Mariusz L, and Aarohan P are employees and shareholders of Eli Lilly and Company; Rebecca C is a former employee and a shareholder of Eli Lilly and Company; Philana F is an employee of Eli Lilly and Company. All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Hsiang Huang, Doctor, MD, PhD, Professor, Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming Yang Ming Chiao Tung University School of Medicine, No. 201, Sec 2, Shi-Pai Road, Taipei 112, Taiwan. yhhuang@vghtpe.gov.tw
Received: September 6, 2021
Peer-review started: September 6, 2021
First decision: October 18, 2021
Revised: November 16, 2021
Accepted: May 26, 2022
Article in press: May 26, 2022
Published online: June 27, 2022
Processing time: 290 Days and 5.8 Hours
Abstract

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. It is an aggressive disease that often progresses rapidly when it fails to respond to treatment. As such, patients have limited opportunities to try different subsequent-line treatment regimens. In the last 5 years, the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased, which has made treatment choices for this patient population increasingly complex. In the second-line setting, several phase III trials of regorafenib (RESORCE), ramucirumab (REACH/REACH-2), and cabozantinib (CELESTIAL) have demonstrated clinically meaningful survival benefits in patients with the disease. However, the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy, with a limited duration of response. Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein (AFP) levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment. Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile. Therefore, it should be considered an option for patients with AFP levels ≥ 400 ng/mL.

Keywords: Hepatocellular carcinoma; Alpha-fetoprotein; Prognostic factor; Ramucirumab; Second-line treatment; Survival

Core Tip: Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease. Identifying any predictive or prognostic factors prior to and during systemic treatment of HCC is critical in determining optimal treatment patterns. Here, we summarize the contributions of the most recently developed treatment options in HCC beyond first line to improve outcomes for these patients.