Moving the needle for oncology dose optimization: A call for action

Clinical and Translational Science, vol. 17, pp. e13859

Abstract

Moving the needle for oncology dose optimization: A call for actionProject Optimus is a major FDA initiative aimed at ensuring dose optimization in oncology drug development, moving away from the maximum tolerated dose paradigm and prospectively characterizing dose-response for efficacy and safety for patient-focused maximization of benefit vs. risk.[1][2][3] Mitigating toxicities and enhancing the overall benefit vs. risk of oncology therapies necessitates dose optimization with a commitment to evaluation of innovative dosing paradigms including individualized approaches, where appropriate.This requires the quantitative integration of pharmacological mechanisms of action, efficacy, and safety in the context of associated population variability.The problem of dose optimization in the context of the mechanism of action, cancer pathophysiology, and associated population variability sits neatly at the intersection of translational/ precision medicine and quantitative clinical pharmacology and is important to approach with a patient-focused mindset.Forums convened on the topic of oncology dose optimization largely engage scientific leaders primarily working on oncology research and development, and cancer medicine.These include workshops organized by Friends of Cancer Research (FOCR), 4 American Society of Clinical Oncology (ASCO), 5,6 American Association for Cancer Research (AACR), 7,8 and the International Society of Pharmacometrics (ISoP) 9 in partnership with the US Food and Drugs Administration (FDA).Of note, some of these efforts have yielded seminal publications 1,2,[10][11][12][13] and White Papers 14 offering initial recommendations, including the availability of a Draft FDA guidance on the topic.15 We posited that the American Society for Clinical Pharmacology and Therapeutics (ASCPT)-as a premier scientific and professional organization for clinical pharmacology and translational medicine-is optimally positioned to host a discussion of opportunities for our constituent disciplines (e.g., translational science, clinical pharmacology, pharmacometrics) to synergistically address this problem with a multidisciplinary approach.

Authors 6

1. Karthik Venkatakrishnan corresponding

   EMD Serono, Inc. (United States) · Merck Healthcare KGaA, Darmstadt (Germany)

   Affiliation as printed

   EMD Serono Research and Development Institute, Inc. Billerica Massachusetts USA

   EMD Serono Research and Development Institute, Inc., Billerica, Massachusetts, USA

2. Priya Jayachandran

   Regeneron (United States)

   Affiliation as printed

   Regeneron Pharmaceuticals, Inc. Tarrytown New York USA

   Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA

3. Shirley K. Seo

   United States Food and Drug Administration · Center for Drug Evaluation and Research

   Affiliation as printed

   Division of Cardiometabolic and Endocrine Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration Silver Spring Maryland USA

   Division of Cardiometabolic and Endocrine Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

   This publication reflects the views of the author and should not be construed to represent FDA's views or policies

4. Piet H. van der Graaf Aachen

   Leiden University

   Affiliation as printed

   Certara Canterbury UK

   Leiden University Leiden The Netherlands

   Certara, Canterbury, UK

   Leiden University, Leiden, The Netherlands

5. John A. Wagner
   Affiliation as printed

   Koneksa Health New York New York USA

   Koneksa Health, New York, New York, USA

6. Neeraj Gupta corresponding
   Affiliation as printed

   Takeda Pharmaceuticals Cambridge Massachusetts USA

   Takeda Pharmaceuticals, Cambridge, Massachusetts, USA