Evaluation of surrogate endpoints in phase III randomized control trials of advanced hepatocellular carcinoma treated...

Overall survival (OS) is recommended as a gold standard endpoint but has some limitations. We aimed to finding more effective surrogate endpoints for advanced hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs).

Three online databases were searched for randomized control trials (RCTs) on HCC, published between January 2015 and July 2023, that evaluated ICIs and reported progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and OS. The correlation between the potential surrogate endpoints and OS was evaluated at the trial, arm, and patient levels. The prediction models were validated in single-arm or non-RCTs. Individual data were collected from a real-world (RW) cohort with advanced HCC underwent ICI monotherapy at three tertiary medical centers in China.

Ten RCTs (6023 participants) with 11 comparisons were included. PFS had a moderately significant association with OS (R² = 0.50, p = 0.014). ORR, DCR, and OS showed weak correlations. On limiting the analysis to ICI monotherapy studies, the correlations of OS with PFS became stronger (R² = 0.85, p = 0.02). The RW cohort also verified that PFS was closely related to OS when patient received with ICI monotherapy.

PFS are recommended as surrogate markers in patients with advanced HCC treated with ICI monotherapy.