Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.

Authors

null

Kyung-Hun Lee

Seoul National University Hospital, Seoul, South Korea

Kyung-Hun Lee , Dae-Won Lee , Myoung-Jin Jang , Tae-Yong Kim , Sae-Won Han , Do-Youn Oh , Seock-Ah Im , Tae-You Kim

Organizations

Seoul National University Hospital, Seoul, South Korea, Seoul National University Hospital, Seoul, Korea South, Seoul National University Hospital, Seoul, Republic of Korea, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea, Internal Medicine, Seoul National University Hospital, Seoul, South Korea, Department of Medicine, Seoul National University Hospital, Seoul, Republic of Korea

Research Funding

Other

Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized 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 Spearman rank correlation coefficient (rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: 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% 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% confidence interval (CI) 0.40 – 0.89, p< 0.001) and the corresponding R2 was 0.42. Conclusions: 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. Along with individual-level analysis more evidences are needed to confirm our finding.

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Abstract Details

Meeting

2017 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel and Hepatobiliary Tract

Track

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Sub Track

Multidisciplinary Treatment

Citation

J Clin Oncol 35, 2017 (suppl 4S; abstract 454)

DOI

10.1200/JCO.2017.35.4_suppl.454

Abstract #

454

Poster Bd #

L16

Abstract Disclosures