Pharmacogenetics- and pharmacogenomics-based rational clinical trial designs in oncology

The rapid evolution of molecular technologies that can identify genetic markers and lead to dissecting the inherent variance of individual cancer biology has had a tangible impact on trial designs in oncology. Rational trial designs based on molecular marker expression coupled with drug–marker interactions have started to be adopted, challenging the previous paradigms of morphology-based, single-arm efficacy studies. This review summarizes novel trials being developed based on molecular predictive factor therapeutics and the potential impact these novel trial designs will have on the practice of oncology in future. A variety of clinical trial designs based on tumor and drug–host genetic interactions are discussed and the example of advanced prostate cancer is used to illustrate the changing landscape of clinical trial designs in cancer.