Cargando…
TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials
BACKGROUND: 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. METHODS: We searched PubMed and Embas...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104893/ https://www.ncbi.nlm.nih.gov/pubmed/27736843 http://dx.doi.org/10.1038/bjc.2016.322 |
_version_ | 1782466811320598528 |
---|---|
author | Lee, Dae-Won Jang, Myoung-Jin Lee, Kyung-Hun Cho, Eun Ju Lee, Jeong-Hoon Yu, Su Jong Kim, Yoon Jun Yoon, Jung-Hwan Kim, Tae-Yong Han, Sae-Won Oh, Do-Youn Im, Seock-Ah Kim, Tae-You |
author_facet | Lee, Dae-Won Jang, Myoung-Jin Lee, Kyung-Hun Cho, Eun Ju Lee, Jeong-Hoon Yu, Su Jong Kim, Yoon Jun Yoon, Jung-Hwan Kim, Tae-Yong Han, Sae-Won Oh, Do-Youn Im, Seock-Ah Kim, Tae-You |
author_sort | Lee, Dae-Won |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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 (r(s)) 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 r(s) value and R(2) value between log (HR(TTP)) and log (HR(OS)) 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 r(s) value between TTP and OS was 0.73 (95% CI 0.40–0.89, P<0.001) and the corresponding R(2) 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. |
format | Online Article Text |
id | pubmed-5104893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51048932017-11-08 TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials Lee, Dae-Won Jang, Myoung-Jin Lee, Kyung-Hun Cho, Eun Ju Lee, Jeong-Hoon Yu, Su Jong Kim, Yoon Jun Yoon, Jung-Hwan Kim, Tae-Yong Han, Sae-Won Oh, Do-Youn Im, Seock-Ah Kim, Tae-You Br J Cancer Clinical Study BACKGROUND: 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. METHODS: 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 (r(s)) 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 r(s) value and R(2) value between log (HR(TTP)) and log (HR(OS)) 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 r(s) value between TTP and OS was 0.73 (95% CI 0.40–0.89, P<0.001) and the corresponding R(2) 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. Nature Publishing Group 2016-11-08 2016-10-13 /pmc/articles/PMC5104893/ /pubmed/27736843 http://dx.doi.org/10.1038/bjc.2016.322 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Clinical Study Lee, Dae-Won Jang, Myoung-Jin Lee, Kyung-Hun Cho, Eun Ju Lee, Jeong-Hoon Yu, Su Jong Kim, Yoon Jun Yoon, Jung-Hwan Kim, Tae-Yong Han, Sae-Won Oh, Do-Youn Im, Seock-Ah Kim, Tae-You TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title | TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title_full | TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title_fullStr | TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title_full_unstemmed | TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title_short | TTP as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
title_sort | ttp as a surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: meta-analysis of randomised controlled trials |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104893/ https://www.ncbi.nlm.nih.gov/pubmed/27736843 http://dx.doi.org/10.1038/bjc.2016.322 |
work_keys_str_mv | AT leedaewon ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT jangmyoungjin ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT leekyunghun ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT choeunju ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT leejeonghoon ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT yusujong ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT kimyoonjun ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT yoonjunghwan ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT kimtaeyong ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT hansaewon ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT ohdoyoun ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT imseockah ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials AT kimtaeyou ttpasasurrogateendpointinadvancedhepatocellularcarcinomatreatedwithmoleculartargetedtherapymetaanalysisofrandomisedcontrolledtrials |