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Meta-Analysis
. 2024 Jan-Dec:23:15330338241305700.
doi: 10.1177/15330338241305700.

PD-1/PD-L1 Inhibitors Plus Antiangiogenic Drugs Versus Sorafenib as the First Line Treatment for Advanced Hepatocellular Carcinoma: A Phase 3 RCTs Based Meta-Analysis

Jun Li  1 , Chun Liao  1 , Zhaohui Liu  1 , Hu Xiong  1 , Jing Cai  2 , Tiande Liu  1
Affiliations
Meta-Analysis

PD-1/PD-L1 Inhibitors Plus Antiangiogenic Drugs Versus Sorafenib as the First Line Treatment for Advanced Hepatocellular Carcinoma: A Phase 3 RCTs Based Meta-Analysis

Jun Li et al. Technol Cancer Res Treat. 2024 Jan-Dec.

Abstract

Background: For advanced hepatocellular carcinoma (HCC), sorafenib remains the established therapy. PD-1/PD-L1 inhibitors plus antiangiogenic drugs (PIAD) as a new therapeutic approach for advanced HCC is still a subject of clinical debate regarding whether they offer improved treatment outcomes. This study was conducted to compare the two treatments in terms of antitumor efficacy and safety.

Methods: Randomized controlled trials (RCTs) comparing PIAD and sorafenib for advanced HCC were retrieved from six databases. Survival (overall survival [OS] and progression-free survival [PFS]) were the main outcomes measured. Secondary endpoints included responses, adverse events (AEs), and effects on quality of life.

Results: Seven studies based on four RCTs (CARES-310, COSMIC-312, IMbrave150, and ORIENT-32) were included. The PIAD group exhibited better OS (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: [0.53, 0.89], P = 0.005), and PFS (HR: 0.60, 95% CI: [0.53, 0.67], P < 0.00001). The survival advantages of OS and PFS were confirmed in almost all subgroups. The PIAD group exhibited higher OS rates at 6-18 months and PFS rates at 6-12 months. Additionally, the objective response rate, disease control rate, complete response, and partial response were higher in PIAD group. The PIAD group had a delayed decline in quality of life, physical functioning, and role functioning. However, the PIAD group experienced more grades 3-5 and serious AEs, along with treatment discontinuation, dose reduction, and dose interruption.

Conclusions: PIAD appears to be better than sorafenib for advanced HCC with better survival and responses. However, its higher rate of AEs requires cautious attention.

Keywords: PD-1/PD-L1 inhibitors; antiangiogenic drugs; hepatocellular carcinoma; meta-analysis; sorafenib.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow chart.
Figure 2.
Figure 2.
Forest plots of overall survival and progression-free survival associated with PIAD versus Sorafenib.
Figure 3.
Figure 3.
Forest plots of responses according to RECIST 1.1 associated with PIAD versus Sorafenib.
Figure 4.
Figure 4.
Forest plots of time to deterioration of quality of life, time to deterioration of physical functioning, and time to deterioration of role functioning associated with PIAD versus Sorafenib.
Figure 5.
Figure 5.
Funnel plots of survival (A), responses (B), the impact on quality of life (C), and safety summary (D).
See this image and copyright information in PMC

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