Abstract
The present study compared the efficacy and safety of regorafenib plus programmed death-1 inhibitors (R-P) with regorafenib monotherapy as second-line therapies for advanced hepatocellular carcinoma (HCC). A systematic search of relevant literature published in PubMed, Embase, Web of Science and Cochrane Library databases until October 2023 was conducted. Two authors independently performed data extraction and screening using standardized protocols. Stata/MP 17.0 was used for the meta-analysis to evaluate the impact of R-P treatment on major outcome indicators, including overall survival, progression-free survival (PFS), tumor response and adverse reactions, in patients with advanced HCC. The results indicated that five cohort studies involving 444 patients with advanced HCC were included. The results revealed that R-P treatment improved overall survival [hazard ratio (HR), 0.61; 95% confidence interval (CI) 0.48-0.77; I(2)=0.0%; P=0.663] and PFS (HR, 0.51; 95% CI 0.41-0.63; I(2)=17.5%; P=0.303). Additionally, it increased the objective response rate (risk ratio, 2.33; 95% CI, 1.49-3.64; I(2)=0.0%; P=0.994) and disease control rate (HR, 1.40; 95% CI, 1.20-1.63; I(2)=0.0%; P=0.892) compared with those of regorafenib. However, R-P treatment was associated with an increased incidence of adverse events, such as hypothyroidism, thrombocytopenia and rash, compared with that in regorafenib. In conclusion, R-P is superior to regorafenib monotherapy in terms of survival benefits and tumor response.