The efficacy and safety of different systemic combination therapies on advanced hepatocellular carcinoma: a systematic review and meta-analysis

Ping Li; Ming Hu; Mei Liu; Xiangyu Ren; Donghong Liu; Jiluo Liu; Jianhua Yin; Xiaojie Tan; Guangwen Cao

doi:10.3389/fonc.2023.1197782

The efficacy and safety of different systemic combination therapies on advanced hepatocellular carcinoma: a systematic review and meta-analysis

Front Oncol. 2023 Sep 25:13:1197782. doi: 10.3389/fonc.2023.1197782. eCollection 2023.

Authors

Ping Li¹, Ming Hu¹, Mei Liu¹, Xiangyu Ren¹, Donghong Liu², Jiluo Liu¹, Jianhua Yin¹, Xiaojie Tan¹, Guangwen Cao¹

Affiliations

¹ Department of Epidemiology, Second Military Medical University, Shanghai, China.
² Department of Hepatic Surgery, The Third Affiliated Hospital of Second Military Medical University, Shanghai, China.

Abstract

Background and aims: Systemic combinations have recently brought significant therapeutic benefits for advanced hepatocellular carcinoma (aHCC). To design the most effective combination regimens, a systematic review (PROSPERO ID: CRD42022321949) was conducted to evaluate the efficacy and safety of systemic combinations on aHCC.

Methods: We retrieved all the studies from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Infrastructure (CNKI) using the Medical Subject Headings (MeSH) terms until December 21, 2022. The effect indicators (hazard ratio [HR], relative risk [RR], and median) were pooled by a fixed- or random-effects model. A subgroup analysis was conducted according to types and specific therapies.

Results: In total, 88 eligible studies were selected from 7249 potential records. Each kind of combination treatment (chemotherapy plus chemotherapy, targeted plus immune checkpoint inhibitor (ICI) therapy, targeted plus chemotherapy, and targeted plus targeted therapy) had a better objective response rate (ORR) in patients with aHCC, compared to the monotherapy mostly with sorafenib (RR: 1.57 [1.44-1.71]; I ^{2 =} 30%). Of those, targeted plus ICI therapy showed better therapeutic efficiency in overall survival (median: 15.02 [12.67-17.38]), progression-free survival (median: 7.08 [6.42-7.74]), and ORR (RR: 1.81 [1.55-2.13]), compared to the monotherapy. Specifically, Atezo plus Beva showed all those benefits. Our pooled result showed all the combinations had increased ≥3 Grade treatment-related adverse events (TrAEs), with an RR of 1.25 [95% CI: 1.15-1.36], compared to the monotherapy.

Conclusion: The systemic combinations, especially targeted plus ICI therapy, including Atezo plus Beva, significantly improve clinical outcomes but increase side effects in patients with aHCC. Future trials should concentrate on improvement in therapeutic efficiency and reduction of toxicity of targeted plus ICI therapy.

Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022321949.

Keywords: advanced hepatocellular carcinoma; efficacy; safety; systemic combination therapy; targeted therapy plus ICI therapy.

Publication types

Systematic Review

Grants and funding

This work was supported by grant 2015CB554006 from the National Key Basic Research Program of China (GC); grants 91529305 (GC), 81520108021 (GC), 81673250 (GC), and 81521091 (GC) from the National Natural Science Foundation of China; grants GWV-10.1-XK17 from the “3-year public health promotion” program of Shanghai Municipal Health Commission (GC); and grant 2022QN021 (PL) from the Youth Fund of Naval Military Medical University.