Exploring and validating surrogate endpoints in colorectal cancer

Center for Statistics, Hasselt University, Agoralaan D, 3590 Diepenbeek, Belgium.
Lifetime Data Analysis (Impact Factor: 0.54). 04/2008; 14(1):54-64. DOI: 10.1007/s10985-007-9079-4
Source: PubMed

ABSTRACT Sargent et al (J Clin Oncol 23: 8664-8670, 2005) concluded that 3-year disease-free survival (DFS) can be considered a valid surrogate (replacement) endpoint for 5-year overall survival (OS) in clinical trials of adjuvant chemotherapy for colorectal cancer. We address the question whether the conclusion holds for trials involving other classes of treatments than those considered by Sargent et al. Additionally, we assess if the 3-year cutpoint is an optimal one. To this aim, we investigate whether the results reported by Sargent et al. could have been used to predict treatment effects in three centrally randomized adjuvant colorectal cancer trials performed by the Japanese Foundation for Multidisciplinary Treatment for Cancer (JFMTC) (Sakamoto et al. J Clin Oncol 22:484-492, 2004). Our analysis supports the conclusion of Sargent et al. and shows that using DFS at 2 or 3 years would be the best option for the prediction of OS at 5 years.

Download full-text


Available from: Junichi Sakamoto, Jul 29, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antibodies are proteins secreted by vertebrates, which bind to specific molecular moieties [1]. Millions of different antibodies are made by organisms, and early in development most self-recognising antibodies are removed from the repertoire. The remaining antibodies, accordingly, recognise non-self molecules, and are used by the host to eliminate microorganisms, foreign objects, and malignant cells. Manufacturing these highly specific molecules and using them for cancer treatment represents a major breakthrough. Nonetheless, the challenges required to bring this technology to the clinic are significant and costly. Drug discovery, manufacturing, and clinical development are all expensive and have high risk [2], and optimising these processes are crucial. This chapter will summarise the science behind this technology, the current use of antibodies in anti-cancer treatment, the methodology of antibody anti-cancer drug development, and the ways in which these components may be improved to facilitate the transition from the laboratory to the clinic.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, the cost of drug development has increased the demands on efficiency in the selection of suitable drug candidates; surrogate end points have emerged to improve this process, hoping that they can help reduce duration and cost of clinical trials. Additionally, they can help in solving ethical issues when measuring the clinical end point involves the application of risky or uncomfortable medical procedures. However, the very mention of surrogate end points has always been controversial, owing in part to unfortunate historical events. As a consequence, there is growing consensus on the use of validated surrogates only. Here, we discuss some of the validation strategies that have recently been proposed and consider the future of surrogate end points in clinical research.
    Expert Review of Pharmacoeconomics & Outcomes Research 06/2008; 8(3):255-9. DOI:10.1586/14737167.8.3.255 · 1.87 Impact Factor
Show more