Personalized Medicine in Oncology Drug Development

Abstract

OverviewThe concept of personalized medicine in oncology drug development is no longer an aspiration; it is now, in large measure, the accepted paradigm of how oncology drugs should be developed. In modern oncology drug development, determining which molecularly characterized tumors will benefit the most from a drug is a critical part of the development plan. In addition, another important personalized medicine approach is emerging whereby a therapeutic is specific to an individual patient. Examples of this individualized therapeutic approach include engineering of autologous immune cells with reinfusion into the patient or cancer vaccines that are specific to an individual tumor.A growing number of successful examples have demonstrated that the personalized medicine approach via biomarker selection can provide more benefit to patients and more rapid approval of drugs. The benefits of a personalized medicine strategy in oncology drug development are multiple and include an increased probability of overall success, smaller phase 3 registration trials, and the potential for enhanced clinical benefits for patients. In a recent review, Falconi and colleagues examined the outcome of 676 phase 1, 2, and 3 clinical trials of novel therapeutics for non‐small‐cell lung cancer (NSCLC) conducted from 1998 to 2012.1Overall, the cumulative success rate, as defined by the advancement to the next stage of clinical testing or to approval, was only 11%. However, when a biomarker was utilized for patient selection, the cumulative success rate increased by nearly sixfold to 62%. Thus, there is strong objective evidence for predictive biomarkers to enhance the probability of success in drug development. Using specific genetic and/or protein markers, a number of important drugs have been developed and approved in specific populations. This approach represents a paradigm shift that has proved so powerful that it is now a standard.The European Society for Medical Oncology has published a Glossary on Precision Medicine2with important definitions. Additionally, a workshop regarding “The drug development paradigm in oncology” was held in Washington DC in December 2016 with the participation of multiple stakeholders (researchers, patient advocates and representatives from industry, academia, and government), and multiple strategies to improve drug development in oncology were discussed.3