Transarterial chemoembolization plus sorafenib versus sorafenib for intermediate-advanced hepatocellular carcinoma A meta-analysis comparing clinical outcomes

Background: Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the second leading cause of cancer-related death worldwide, local and systemic therapies are beneficial for those who have more advanced disease or are not suitable for radical treatment. We aim to investigate the clinical outcomes of transarterial chemoembolization (TACE) plus sorafenib compared with sorafenib monotherapy for intermediate-advanced HCC. Methods: A systematic search according to preferred reporting items for systematic reviews and meta-analyses guidelines in the PubMed database was conducted from inception to December 31, 2020 for published studies comparing survival outcomes and tumor response between TACE + sorafenib and sorafenib alone for intermediate-advanced HCC. Results: Five eligible cohort studies and a randomized controlled trial with a total of 3015 patients were identified. We found that the TACE + sorafenib group had a significantly better overall survival (OS) (hazard ratio, 0.77; 95% confidence interval [CI] 0.66-0.88, P < .001) than those treated with sorafenib. Median OS ranged from 7.0 to 22.0 months with TACE + sorafenib and from 5.9 to 18.0 months with sorafenib. The combination of TACE + sorafenib had a significantly better time to progression (hazard ratio, 0.74; 95% CI 0.65-0.82, P < .001) than those treated with sorafenib. Median time to progression ranged from 2.5 to 5.3 months with TACE + sorafenib and from 2.1 to 2.8 months with sorafenib. The results showed the TACE + sorafenib group had a higher disease control rate (log odds ratio, 0.52; 95% CI 0.25-0.80, P = .0002), objective response rate (log odds ratio, 0.85; 95% CI 0.37-1.33, P = .0006) than sorafenib group. Hand-foot skin reaction, diarrhea, fatigue, vomiting, and alanine aminotransferase (ALT) elevation were common adverse events. The adverse events were similar between the 2 groups excluding elevated ALT. Conclusion: Although the TACE + sorafenib group had a higher elevated ALT, the combination of TACE + sorafenib had an OS benefit compared with sorafenib in the treatment of intermediate-advanced HCC. Further research is necessary to affirm this finding and clarify whether certain subgroups benefit from different combinations between TACE and sorafenib.