Efficacy and Safety of PD-1/PD-L1 Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Yuwei Liu; Jiahui Pan; Fangbo Gao; Wentao Xu; Hongyu Li; Xingshun Qi

doi:10.1007/s12325-022-02371-3

Efficacy and Safety of PD-1/PD-L1 Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis

Adv Ther. 2023 Feb;40(2):521-549. doi: 10.1007/s12325-022-02371-3. Epub 2022 Nov 18.

Authors

Yuwei Liu^{1

2}, Jiahui Pan^{1

2}, Fangbo Gao^{1

2}, Wentao Xu^{1

2}, Hongyu Li¹, Xingshun Qi³

Affiliations

¹ Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, No. 83 Wenhua Road, Shenyang, 110840, Liaoning, People's Republic of China.
² Postgraduate College, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
³ Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, No. 83 Wenhua Road, Shenyang, 110840, Liaoning, People's Republic of China. xingshunqi@126.com.

PMID: 36399316
DOI: 10.1007/s12325-022-02371-3

Abstract

Introduction: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly employed for the treatment of various cancers in clinical practice. This study aimed to systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for advanced hepatocellular carcinoma (HCC).

Methods: PubMed, EMBASE, Cochrane library, Web of Science, and Abstracts of American Society of Clinical Oncology proceedings databases were searched. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), median overall survival (OS), and incidence of adverse events (AEs) and drug withdrawal were pooled. Odds ratio (OR) and hazard ratio (HR) were calculated to analyze the difference in the ORR, DCR, PFS, and OS between groups.

Results: Among the 14,902 initially identified papers, 98 studies regarding use of PD-1/PD-L1 inhibitors in advanced HCC were included. Based on different criteria of response in solid tumors, the pooled ORR, DCR, and median PFS was 16-36%, 54-74%, and 4.5-6.8 months, respectively. The pooled median OS was 11.9 months. Compared to multitarget tyrosine kinase inhibitors (TKIs), PD-1/PD-L1 inhibitors monotherapy significantly increased ORR (OR 2.73, P < 0.00001) and OS (HR 0.97, P = 0.05), and PD-1/PD-L1 inhibitors combined with TKIs significantly increased ORR (OR 3.17, P < 0.00001), DCR (OR 2.44, P < 0.00001), PFS (HR 0.58, P < 0.00001), and OS (HR 0.58, P < 0.00001). The pooled incidence of all-grade AEs, grade ≥ 3 AEs, and drug withdrawal was 71%, 25%, and 7%, respectively.

Conclusion: On the basis of the present systematic review and meta-analysis, PD-1/PD-L1 inhibitors should be the preferred treatment choice for advanced HCC owing to their higher antitumor effect and improved outcomes.

Keywords: Adverse event; Disease control rate; Meta-analysis; Objective response rate; Overall survival; PD-1; PD-L1; Progression-free survival.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immune Checkpoint Inhibitors / adverse effects
Liver Neoplasms* / drug therapy
Lung Neoplasms* / drug therapy
Programmed Cell Death 1 Receptor

Substances

Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor