Ye Rim Kim, Euichang Kim, Ha Il Kim, Seungbong Han, Jihyun An, Ju Hyun Shim
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引用次数: 0
Abstract
Background and aims: We conducted an updated network meta-analysis to evaluate and identify the optimal first-line treatment for advanced hepatocellular carcinoma (HCC) among all relevant interventional and targeted therapies.
Methods: We analyzed 16 phase 2 or 3 randomized controlled trials involving 9,482 patients with metastatic or unresectable HCC published between 2018 and 2024. The trials evaluated 11 systemic agents and 5 interventional treatments in combination with systemic therapy, using either sorafenib or lenvatinib as the control. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS) and grade 3-4 adverse events. Subgroup analyses were conducted to assess individual treatment efficacies in specific clinical settings.
Results: Transarterial chemoembolization (TACE) combined with lenvatinib provided the greatest improvement in OS over sorafenib, with a hazard ratio of 0.41 (95% confidence interval, 0.30-0.58), followed by sintilimab + IBI305 (0.57; 0.43-0.75), camrelizumab + rivoceranib (0.62; 0.48-0.80), atezolizumab + bevacizumab (0.66; 0.51-0.85), lenvatinib + pembrolizumab (0.77; 0.62-0.97), and tremelimumab + durvalumab (0.78; 0.64-0.95). These combinations, except for tremelimumab + durvalumab, also showed significantly superior PFS to sorafenib. TACE + lenvatinib was ranked first in OS analyses with the other current standard-of-care regimens (lenvatinib, atezolizumab + bevacizumab, and tremelimumab + durvalumab) as controls. TACE + lenvatinib, sintilimab + IBI305, and atezolizumab + bevacizumab demonstrated consistently significant extension of OS over sorafenib in subsets with portal invasion, extrahepatic metastasis, and hepatitis B. All immunotherapy-based combinations were significantly associated with a higher risk of adverse events than sorafenib.
Conclusions: For advanced HCC, our first-line analysis consistently scored TACE + lenvatinib the best for survival outcomes, followed by various immunotherapy-based combinations. However, the superior efficacy of TACE + lenvatinib should be interpreted with consideration of its derivation from a region with high hepatitis B virus prevalence.
期刊介绍:
Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.