Weak correlation of overall survival and time to progression in advanced hepatocellular carcinoma.

233 Background: Time to progression (TTP) is a potential surrogate endpoint in oncology clinical trials. The correlation of TTP and overall survival (OS) in advanced hepatocellular carcinoma (HCC) has been studied by meta-analyses (Terashima et al, Hepatol Res 2016;46:650); however, these analyses may be biased by trial selection and heterogeneity. We assessed the correlation between TTP and OS using simulated trials based on patient level data from 2 large sorafenib trials in patients (pts) with unresectable HCC (uHCC). Methods: To assess the correlation between OS and TTP, a bootstrap approach was applied to simulate 10,000 trials based on data from the randomized, phase III sorafenib trials in uHCC pts (SHARP [n = 602] and Asia-Pacific [AP; n = 226]). Individual data correlation between OS and TTP was conducted for 828 pts included in SHARP and AP. Pearson correlation was calculated between estimated median OS (mOS) and estimated median TTP (mTTP) for sorafenib and placebo (PLA) arms separately. Pearson correlation of log rank test statistics and hazard ratios were calculated to compare sorafenib and PLA for OS and TTP. Results: Simulated mOS and mTTP trial data were similar to that reported in SHARP and AP (Table). In SHARP, the correlation between mOS and mTTP was 0.270 for sorafenib and 0.218 for PLA, and in AP, 0.333 for sorafenib and 0.251 for PLA. The correlation of log rank test statistics comparing sorafenib and PLA was 0.387 in SHARP and 0.540 in AP. Conclusions: The simulated mOS/mTTP data was representative of pt population data in SHARP and AP. Our analysis showed a weak correlation between OS and TTP. This finding challenges TTP as a surrogate endpoint in HCC and should be considered when interpreting TTP results for the evaluation of treatment effect in uHCC. These data reinforce that the pattern of progression is potentially more relevant to OS than tumor progression as suggested by Reig et al ( Hepatol 2013;58:2023). Clinical trial information: NCT00105443; NCT00492752. [Table: see text]