Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective
- 19 February 2008
- journal article
- research article
- Published by SAGE Publications in Statistical Methods in Medical Research
- Vol. 17 (5), 519-527
- https://doi.org/10.1177/0962280207081865
Abstract
Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a “valid” surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful. The term `surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words `surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words `surrogate and heart' are entered into PubMed, suggesting that the issue of surrogate endpoints goes beyond the field of oncology, although the frequency of discussion varies (Figure 1; note different y-axis scales for oncology and cardiology). The goal of the present paper is to discuss the main issues surrounding surrogate endpoints from a clinician's point of view, using as an example surrogate endpoints of overall survival (OS) in advanced colorectal cancer (ACC).This publication has 25 references indexed in Scilit:
- Response rate or time to progression as predictors of survival in trials of metastatic colorectal cancer or non-small-cell lung cancer: a meta-analysisThe Lancet Oncology, 2006
- Randomized Controlled Trial of Reduced-Dose Bolus Fluorouracil Plus Leucovorin and Irinotecan or Infused Fluorouracil Plus Leucovorin and Oxaliplatin in Patients With Previously Untreated Metastatic Colorectal Cancer: A North American Intergroup TrialJournal of Clinical Oncology, 2006
- Second-Line Treatment of Patients With Metastatic Colorectal CancerSeminars in Oncology, 2005
- Objective Response Rate As a Surrogate End Point: A CommentaryJournal of Clinical Oncology, 2005
- Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal CancerThe New England Journal of Medicine, 2004
- The validation of surrogate endpoints in meta-analyses of randomized experimentsBiostatistics, 2000
- ESTIMATING THE PROPORTION OF TREATMENT EFFECT EXPLAINED BY A SURROGATE MARKERStatistics in Medicine, 1997
- Perspective: Validating Surrogate Markers--Are We Being Naive?The Journal of Infectious Diseases, 1997
- Statistical validation of intermediate endpoints for chronic diseasesStatistics in Medicine, 1992
- Surrogate endpoints in clinical trials: Definition and operational criteriaStatistics in Medicine, 1989