The use of biomarkers in cancer clinical trials


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Marc Buyse
International Drug Development Institute, Brussels, Belgium

Abstract

<p>Biomarkers can be classified into three broad groups: (a) prognostic biomarkers, which affect the outcome of patients in terms of a clinical endpoint, (b) predictive biomarkers, which affect the effect of a specific treatment on a clinical endpoint, and (c) surrogate biomarkers, which aim at replacing a clinical endpoint in clinical trials carried out to evaluate the effect of a specific treatment. They can be measured once before a treatment is administered, or repeatedly before, during and after the treatment is administered, in which case interest focuses on changes in the biomarkers over time.</p><p>Biomarkers are already in common use for patient management: PSA is used to monitor progression of disease in prostate cancer, CEA in colorectal cancer, etc. However, this does not automatically imply that these biomarkers are useful for clinical research purposes. In terms of clinical development of new treatments, biomarkers can be used to select patients eligible for clinical trials, to stratify patients at entry in clinical trials, to monitor patients and guide treatment decisions, or to substitute for a clinical endpoint in the evaluation of the effects of new treatments. Prognostic biomarkers are useful primarily to adjust therapy, with patients of poor prognosis being treated more aggressively than patients of good prognosis. Predictive factors can be used to select subsets of patients who derive the most benefit (or the least toxicity) from a new treatment, in order to limit clinical trials to this subset. A surrogate biomarker should be capable, in and of itself, to predict that a new treatment will have a desired effect on the ultimate endpoint of interest, and hence permit a conclusion to be reached with far less patients and shorter follow-up. Currently, no such biomarkers have been identified in oncology. This talk will review all these issues through recent examples.</p><br>