Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and
Di Wu1, Binyang Jia2, Muyuan Jia3
1Department of Otolaryngology, Head and Neck Surgery, Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang, China.
Background:
In recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.
Methods:
This study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).
Conclusion:
In the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.
Systematic Review Registration:
https://www.crd.york.ac.uk/prospero, identifier CRD42023440173.
Insights
For advanced hepatocellular carcinoma, combining PD-1 inhibitors with bevacizumab or TKIs is effective for first-line treatment. Regorafenib and cabozantinib are top second-line choices, improving survival in advanced HCC.
Area of Science:
- Hepatobiliary Cancers
- Medical Oncology
- Immunotherapy
Background:
- Advanced hepatocellular carcinoma (HCC) treatment has rapidly evolved with new systemic agents.
- Head-to-head comparisons are lacking, complicating treatment selection.
- Efficacy and safety profiles of various advanced HCC therapies require elucidation.
Approach:
- A network meta-analysis synthesized data from 23 randomized controlled trials.
- Included 15 first-line and 8 second-line treatment regimens.
- Total of 14,703 patients with advanced HCC were analyzed.
Key Points:
- First-line: PD-1 inhibitor + bevacizumab improved overall survival. PD-1 inhibitor + TKI or bevacizumab enhanced progression-free survival.
- Second-line: All agents improved progression-free survival vs. placebo. Cabozantinib ranked highest for PFS.
- Overall survival benefit in second-line was seen with cabozantinib, regorafenib, ramucirumab, and pembrolizumab; regorafenib ranked highest.
Conclusions:
- Immune checkpoint inhibitor + bevacizumab and immune checkpoint inhibitor + TKI are top first-line options for advanced HCC.
- Dual immunotherapy is preferred if VEGF inhibitors are contraindicated.
- Regorafenib and cabozantinib are the most effective second-line treatments for advanced HCC.
More Related Videos
Related Concept Videos
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...