Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis

Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI.Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation.74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14-18%) and 52% (95% CI: 47-57%), and the median PFS and OS were 3.75 (95% CI: 2.88-4.90) months, and 13.20 (95% CI: 11.88-14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p < 0.05), 0.43 (R2 = 0.18, p < 0.05), and 0.50 (R2 = 0.33, p < 0.05), respectively. Further, the association between PFS and OS of the combination strategy showed a better correlation (rs = 0.79, R2 = 0.75, p < 0.05).These results suggest that PFS could be potential surrogates for OS, especially PFS for patients who treated with ICI combination regimen.