Terashima Takeshi, Yamashita Tatsuya, Toyama Tadashi, Arai Kuniaki, Kawaguchi Kazunori, Kitamura Kazuya, Yamashita Taro, Sakai Yoshio, Mizukoshi Eishiro, Honda Masao, Kaneko Shuichi
Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.
Department of Nephrology, Kanazawa University Hospital, Kanazawa, Japan.
Liver Cancer. 2019 Mar;8(2):130-139. doi: 10.1159/000489505. Epub 2018 Jun 14.
Time to progression (TTP) is widely used as the endpoint in early-phase trials of advanced hepatocellular carcinoma (HCC). However, the relevance of using TTP as a surrogate marker for overall survival (OS) in pivotal trials remains uncertain. The PubMed database and ASCO Meeting Library were searched for reports of randomized controlled trials that investigated patients with advanced HCC, included data for both OS and TTP, and were launched between 2009 and 2016. The correlation between hazard ratios (HRs) for TTP and OS was determined using weighted linear regression. Correlations between median OS and TTP, and between median OS and postprogression survival (PPS), defined as the period obtained by subtracting the median TTP from the median OS, were also evaluated. The database search yielded 24 trials with 50 arms. Overall, TTP HR correlated with OS HR ( = 0.73); however, the coefficient in the regression equation was 0.48. The correlation between median OS and median TTP was not so strong ( = 0.50), whereas the correlation between median OS and median PPS was strong ( = 0.78). In advanced HCC, the OS HR can be predicted from the TTP HR, which is useful when considering whether to proceed to a pivotal trial based on the results of early-phase trials. TTP may be a better endpoint than OS for evaluating a novel agent in a pivotal trial, because an improvement in antitumor effect cannot fully reflect an improvement in OS due to the strong impact of PPS on OS.
疾病进展时间（TTP）在晚期肝细胞癌（HCC）的早期试验中被广泛用作终点指标。然而，在关键试验中使用TTP作为总生存期（OS）替代标志物的相关性仍不确定。检索了PubMed数据库和美国临床肿瘤学会会议文库，以查找关于晚期HCC患者的随机对照试验报告，这些报告包含OS和TTP的数据，且于2009年至2016年期间开展。使用加权线性回归确定TTP和OS风险比（HR）之间的相关性。还评估了中位OS与TTP之间以及中位OS与进展后生存期（PPS，定义为中位OS减去中位TTP所得到的时间段）之间的相关性。数据库检索得到24项试验共50个研究组。总体而言，TTP HR与OS HR相关（ = 0.73）；然而，回归方程中的系数为0.48。中位OS与中位TTP之间的相关性不是很强（ = 0.
