Advances in oncology research have led to an influx of new cancer therapies that can precisely target the molecular underpinnings of a patient’s disease. Such therapies are the foundation of the movement toward precision medicine, which aims to deliver the right therapy to the right patient at the right time. The rapid progress in cancer drug discovery research—based on the improved understanding of the molecular and genetic basis of disease—has the potential to increase the number of targeted therapies for patients with cancer. However, there are concerns that the traditional drug development paradigm may impede the assessment and regulatory approval of new targeted therapies for cancer. Compared with traditional cytotoxic chemotherapies, new targeted therapies for cancer may demonstrate early evidence of clear benefit that make the traditional approach to drug development inefficient and even unethical if equipoise is lost. Thus, there is substantial interest in improving the methods of drug development, especially when therapies demonstrate substantial effectiveness early in the development process or for diseases that currently lack satisfactory treatment options.
Typically, new drug development includes three discrete, linear phases (phase 1, 2, and 3) to collect the necessary data for review and approval by the Food and Drug Administration (FDA) approval. These traditional phases can also include phase 0 for exploratory studies and phase 4 for postmarketing surveillance. FDA has four programs to expedite the development and approval of therapies, which include fast track, breakthrough therapy, priority review designations, and accelerated approval. Although these programs vary, therapies expedited through these programs are intended for serious diseases with consideration of whether there is an unmet medical need or whether the therapy under consideration provides a significant advantage over existing therapies. In line with these expedited mechanisms intended to improve development and review processes for specific therapeutic agent development, there are also calls for more flexible, efficient mechanisms of cancer drug development and review in general. Staff from the FDA Office of Oncology Products recently authored an article outlining an evolving drug development paradigm, indicating their willingness to consider alternatives to the traditional phased drug development process.
Given the potential for advances in cancer research and drug development to improve patient outcomes, there is an urgent need to reexamine the scientific and regulatory approach to developing new cancer therapies to ensure that patients ultimately benefit from these advances. Improving the efficiency of the drug development and regulatory review process, while ensuring the safety of new therapies, will be critical to speeding more effective therapies to patients with cancer.
This workshop examined the challenges to achieving this goal and provided an opportunity for patients, clinicians, and drug developers to share ideas for actions to improve the process. Workshop participants discussed challenges with the traditional phased drug development paradigm in the age of targeted therapies, best practices for cancer drug development and review, lessons learned from recent expedited drug approval processes, and evidence requirements for cancer therapies before and after regulatory approval, as well as the mechanisms needed to generate this knowledge.
This workshop was conducted in collaboration with the Forum on Drug Discovery, Development, and Translation. For more information on the Forum, you can visit: https://www.nationalacademies.org/our-work/forum-on-drug-discovery-development-and-translation.
For full videos of the entire workshop, you can visit: December 2016 - The Drug Development Paradigm in Oncology.
Workshop Planning Committee
Richard Schilsky, Chair, American Society of Clinical Oncology
Amy Abernethy, Flatiron Health
Jeff Allen, Friends of Cancer Research
Kenneth Anderson, Dana-Farber Cancer Institute
Margaret Anderson, FasterCures
Monica Bertagnolli, Dana-Farber Cancer Institute
Gideon Blumenthal, Food and Drug Administration
Hedvig Hricak, Memorial Sloan Kettering Cancer Center
Ronald Kline, Centers for Medicare and Medicaid Services
Amy McKee, Food and Drug Administration
Rebecca Pentz, Emory School of Medicine
Steven Piantadosi, Cedars-Sinai Medical Center
Mace Rothenberg, Pfizer
Daniel Sargent, Mayo Clinic Cancer Center
Deborah Schrag, Dana-Farber Cancer Institute
Marc Theoret, Food and Drug Administration
Suzanne Topalian, Johns Hopkins Kimmel Cancer Center
Confirmed Speakers and PanelistsAmy Abernethy, Flatiron Health
Kenneth Anderson, Dana-Farber Cancer Institute
Gideon Blumenthal, Food and Drug Administration
Jeffrey Brown, Harvard Pilgrim Health Care Institute
Howard A. Burris, III, Sarah Cannon Research Institute
David Feltquate, Bristol-Myers Squibb
Richard Finn, UCLA Jonsson Comprehensive Cancer Center
Keith Flaherty, Massachusetts General Hospital
R. Donald Harvey, Emory School of Medicine
Hedvig Hricak, Memorial Sloan Kettering Cancer Center
Gwynn Ison, Food and Drug Administration
Elizabeth Jaffee, Sidney Kimmel Comprehensive Cancer Center
Pasi Jänne, Dana-Farber Cancer Institute
Steve Joffe, University of Pennsylvania
Patricia Keegan, Food and Drug Administration
Ronald Kline, Centers for Medicare and Medicaid Services
Maria Koehler, Pfizer Oncology
Steven Lemery, Food and Drug Administration
Lynn M. Matrisian, Pancreatic Cancer Action Network
Amy McKee, Food and Drug Administration
Rebecca Pentz, Emory School of Medicine
Steven Piantadosi, Cedars-Sinai Medical Center
G. K. Raju, Massachusetts Institute of Technology
Mark Ratain, University of Chicago
Mary Redman, Fred Hutchinson Cancer Research Center
Frank Rockhold, Duke Clinical Research Institute
Mace Rothenberg, Pfizer
Eric Rubin, Merck Research Laboratories
Ellen Sigal, Friends of Cancer Research
Rajeshwari Sridhara, Food and Drug Administration
Marc Theoret, Food and Drug Administration
Wolfgang Weber, Memorial Sloan Kettering Cancer Center
Janet Woodcock, Food and Drug Administration