41IN - Where Next for Precision Medicine for Prostate Cancer?

Abstract

ABSTRACT The approval of new agents for the treatment of men with prostate cancer has raised expectations of an even greater improvement in outcomes. To meet these expectations, we will need to transition from the prevailing drug development strategy to a therapy development paradigm. The Therapy Development Paradigm integrates the understanding of prostate cancer biology with determinants of response to inform marker-driven combinatorial treatment strategies. To achieve therapy development we must link the understanding of the biology to clinical decision through biomarkers. We are called to catalyze the transition from a prognostic to a predictive model for therapy development, complementing the traditional “disease state model” which focuses on controlling, relieving, or eliminating poor outcomes as the basis for continuing therapy. To achieve this goal, we must leverage the emerging knowledge of prostate cancer biology and build on novel tissue acquisition methodologies, trial designs, and co–clinical investigations. Prostate Cancer is an exception to other adult solid tumors. Notwithstanding the known disease heterogeneity we continue to treat it as a uniform disease unlike progress made in treating other common adult solid tumor such breast colorectal and lung cancer. There is a clear understanding that responsiveness to hormones is an important prognosticator of outcome throughout the spectrum of this disease as this has recently been extended to the castrate resistant state with the advent of onovel androgen signaling inhibitors. This parallels the improved understanding of the driver of aggressive variants i.e “anaplastic disease”. These foundational observations that reflect the drive biology in the extremes will allow us to dissect the complexity of prostate cancer and allow us to perform enrichment studies. Moreover developing and validating predictive markers that anticipate the adaptive responses to therapy that account for the emergence of CRPC and apply them in secondary prevention strategies will avoid or greatly delay the emergence of resistance that occurs in most men treated with m-CRPC. Confirmation of these studies will lead to more precise allocation of therapy in individual patients at the right time in progression accounting for the striking temporal heterogeneity of prostate cancer. Disclosure: E. Efstathiou: Pharma Sponsored Research JnJ - Janssen, Astellas, Millenium, Viamet, Sanofi Ad Board, Steering Committee, Speaker's bureau Jnj-Janssen, Astellas, Millenium, Sanofi, Bayer.