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Br J Cancer. 2016 Nov 8;115(10):1201-1205. doi: 10.1038/bjc.2016.322. Epub 2016 Oct 13.

TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials.

Lee DW1, Jang MJ2, Lee KH1,3, Cho EJ1,4, Lee JH1,4, Yu SJ1,4, Kim YJ1,4, Yoon JH1,4, Kim TY1,3, Han SW1,3, Oh DY1,3, Im SA1,3, Kim TY1,3.

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Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Medical Research Collaborating Center, Seoul National University Hospital, Seoul, South Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.



Time to progression (TTP) is suggested as a reliable endpoint compared with the progression-free survival in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied.


We searched PubMed and Embase data to obtain data source. Eligible studies were randomised controlled phase III trials, which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by the Spearman rank correlation coefficient (rs) and linear regression analysis. The association between median TTP and OS was also investigated.


Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% confidence interval (CI) 0.12-0.94, P=0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% CI 0.40-0.89, P<0.001) and the corresponding R2 was 0.42.


Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS.

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