10 - Surrogate end Points and Biomakers for Early Trials of Novel Anticancer Agents

Abstract

This chapter discusses surrogate end points and biomarkers for early trials of novel anticancer agents. A number of agents have been developed to selectively target aberrant molecular pathways in cancer cells. It is found that because of this selective targeting, these agents tend to be less toxic when compared to standard cytotoxic chemotherapy agents. Their toxicity profile tends to be different from that of cytotoxic agents. The presence of the target must correlate with clinical benefit when the drug is employed and blocking the target should impair tumor growth. As a pharmacodynamic marker, a surrogate end-point may help to reliably establish a dosing schedule in phase I studies. Surrogate endpoints can provide proof of in vivo effects that complement traditional pharmacokinetic studies. Biomarkers can be used as predictive factors to identify patients likely to respond to a particular therapeutic agent. The expression of estrogen and progesterone receptors on breast cancer cells is a predictive marker for response to tamoxifen and aromatase inhibitors. The presence of a biomarker would correlate with the clinical outcome of a patient. The end point of a clinical trial to evaluate a prognostic factor should be survival, or some other clinical parameter such as time to progression.