Combinatorial treatment with traditional medicinal preparations and VEGFR-tyrosine kinase inhibitors for middle-advanced primary liver cancer: A systematic review and meta-analysis.

Background: This study aimed to investigate the therapeutic efficacy and safety of Traditional medicine preparations (TMPs) given in combination with vascular endothelial growth factor receptor (VEGFR)-associated multi-targeted tyrosine kinase inhibitors (TKIs) for the treatment of middle to advanced-stage primary liver cancer (PLC).

Methods: This systematic literature survey employed 10 electronic databases and 2 clinical trial registration platforms to identify relevant studies on the use of TMPs + VEGFR-TKIs to treat patients with middle-advanced PLC. Furthermore, a meta-analysis was performed following the PRISMA guidelines using the risk ratio (RR) at 95% confidence intervals (CI) or standardized mean difference as effect measures.

Results: A total of 26 studies comprising 1678 middle-advanced PLC patients were selected. The meta-analysis revealed that compared with VEGFR-TKI mono-treatment, the co-therapy of TMPs + VEGFR-TKIs considerably enhanced the objective response rate (RR = 1.49, 95% CI: 1.31-1.69), disease control rate (RR = 1.23, 95% CI: 1.16-1.30), and one-year overall survival (RR = 1.49, 95% CI: 1.28-1.74). Furthermore, the co-therapy was associated with reduced incidences of liver dysfunction (RR = 0.64, 95% CI: 0.45-0.91), proteinuria (RR = 0.43, 95% CI: 0.24-0.75), hypertension (RR = 0.66, 95% CI: 0.53-0.83), hand-foot skin reactions (RR = 0.63, 95% CI: 0.49-0.80), myelosuppression (RR = 0.63, 95% CI: 0.46-0.87), and gastrointestinal reactions (RR = 0.64, 95% CI: 0.45-0.92). Moreover, the co-therapy indicated no increase in the incidences of rash and fatigue.

Conclusion: This systematic analysis revealed that co-therapy with TMPs + VEGFR-TKIs has a higher effectiveness and safety profile for treating middle-advanced PLC patients. However, further validation using randomized control trials is required.

Prospero Registration No: CRD42022350634.