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Efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of
Fenping Lu1,2, Kai Zhao3, Miaoqing Ye4
1Beijing University of Chinese Medicine, Beijing, China.
Background:
The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC).
Methods:
We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability.
Results:
We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures.
Conclusions:
Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.
Insights
Regorafenib and cabozantinib are the top second-line treatments for advanced liver cancer (HCC) after initial therapy failure. This network meta-analysis compared 10 treatments, finding these two offered the best overall efficacy and safety profiles.
Area of Science:
- Hepatology and Oncology
- Clinical Trial Analysis
- Network Meta-Analysis
Background:
- Selecting second-line therapy for liver cancer (HCC) after first-line treatment failure is challenging due to limited comparative data.
- Network meta-analysis (NMA) offers a robust approach to systematically evaluate outcomes and adverse effects of various second-line HCC treatments.
Purpose of the Study:
- To systematically evaluate and compare the clinical outcomes and safety of various second-line treatments for advanced hepatocellular carcinoma (HCC) using a network meta-analysis.
Main Methods:
- A systematic literature search was conducted across major databases (PubMed, Embase, Web of Science, Cochrane Library) for phase III/IV randomized controlled trials (RCTs) up to March 2024.
- Extracted outcomes included overall survival (OS), progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse events.
- The study was registered (CRD42023427843) to ensure transparency and reliability.
Main Results:
- The analysis included 16 RCTs with 7,005 patients and 10 second-line treatments.
- Regorafenib and cabozantinib demonstrated the best overall survival (OS) and progression-free survival (PFS) benefits compared to placebo.
- Ramucirumab and S-1 showed significant increases in objective response rate (ORR), while apatinib and cabozantinib improved disease control rate (DCR). Tivantinib showed safety advantages.
Conclusions:
- Regorafenib and cabozantinib emerge as the optimal second-line treatment choices for patients with advanced HCC, balancing efficacy and safety.
- These findings provide valuable guidance for clinicians managing advanced HCC after first-line treatment failure.
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