Validation of treatment induced specific adverse effect as a predictor of treatment benefit: A case study of NCIC CTG BR21

The target of novel signal transduction inhibitors may be present on normal as well as tumor cells, resulting in mechanistic adverse effects (AE) in addition to antitumor activity. As those AEs lie in the causal pathway that patients respond to the drug, may thus serve as an indicator of benefit from the drug. In this paper, we discuss issues in validating drug related AEs as predictive markers of overall survival benefit. Based on our proposed approach, we showed that erlotinib induced skin rash appears to predict a survival benefit.