» Articles » PMID: 32898239

Optimizing Survival and the Changing Landscape of Targeted Therapy for Intermediate and Advanced Hepatocellular Carcinoma: A Systematic Review

Overview
Specialty Oncology
Date 2020 Sep 8
PMID 32898239
Citations 27
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Systemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice.

Methods: Published and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms "hepatocellular cancer" AND "advanced" AND "targeted therapy" AND "phase III" OR respective aliases (PRISMA).

Results: Ten phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lenvatinib demonstrated non-inferior OS. Following progression on sorafenib, statistically significant OS improvements over placebo were seen for cabozantinib and regorafenib in unselected patients and for ramucirumab in those with baseline α-fetoprotein≥400 ng/mL. Based on improved OS and PROs, atezolizumab plus bevacizumab appears to be a preferred first-line treatment option for intermediate or advanced non-LRT eligible HCC. Phase III data informing sequencing of later lines of treatment is lacking. Therefore, sequencing principles are proposed that can be used to guide treatment selection.

Conclusions: Ongoing trials will continue to inform optimal therapy. Multiple targeted therapies have improved OS in intermediate or advanced non-LRT eligible HCC, although optimal sequencing is an area of ongoing investigation.

Citing Articles

The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy.

Dong H, Zhang Z, Ni M, Xu X, Luo Y, Wang Y Curr Treat Options Oncol. 2024; 25(10):1239-1256.

PMID: 39259476 PMC: 11485193. DOI: 10.1007/s11864-024-01246-9.


Advancements in Immunotherapeutic Treatments for Hepatocellular Carcinoma: Potential of Combination Therapies.

Zarlashat Y, Mushtaq H, Pham L, Abbas W, Sato K Int J Mol Sci. 2024; 25(13).

PMID: 38999940 PMC: 11241106. DOI: 10.3390/ijms25136830.


Efficacy and Safety Analysis of Transarterial Chemoembolization Plus Donafenib With or Without Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Prospective, Single-Arm, Single-Center, Phase II Clinical Study.

Li J, Li Y, Song J, Zhao L J Hepatocell Carcinoma. 2024; 11:1207-1219.

PMID: 38946843 PMC: 11214825. DOI: 10.2147/JHC.S473617.


Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.

Zhu D, Su K, Ou-Yang X, Zhang Y, Yu X, Li Z Mol Cell Biochem. 2024; 479(7):1553-1570.

PMID: 38856795 PMC: 11254988. DOI: 10.1007/s11010-024-05040-x.


Multilayered insights: a machine learning approach for personalized prognostic assessment in hepatocellular carcinoma.

Zhang Z, Du Y, Wei S, Pei W Front Oncol. 2024; 13:1327147.

PMID: 38486931 PMC: 10937467. DOI: 10.3389/fonc.2023.1327147.


References
1.
Vogel A, Cervantes A, Chau I, Daniele B, Llovet J, Meyer T . Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv238-iv255. DOI: 10.1093/annonc/mdy308. View

2.
Ryerson A, Eheman C, Altekruse S, Ward J, Jemal A, Sherman R . Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer. 2016; 122(9):1312-37. PMC: 4840031. DOI: 10.1002/cncr.29936. View

3.
Richani M, Kolly P, Knoepfli M, Herrmann E, Zweifel M, von Tengg-Kobligk H . Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm. Ann Hepatol. 2015; 15(1):82-90. DOI: 10.5604/16652681.1184233. View

4.
Zhu A, Kudo M, Assenat E, Cattan S, Kang Y, Lim H . Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA. 2014; 312(1):57-67. DOI: 10.1001/jama.2014.7189. View

5.
Kudo M, Han K, Ye S, Zhou J, Huang Y, Lin S . A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements. Liver Cancer. 2020; 9(3):245-260. PMC: 7325125. DOI: 10.1159/000507370. View