National Cancer Policy Summit

National Cancer Policy Summit: Setting Priorities for the Next 3 Years

By Margot J. Fromer
December 15, 2013, Volume 4, Issue 20



"Welcome to the meeting we hold every 3 years to choose our next projects,” said John Mendelsohn, MD, Chair of the National Cancer Policy Forum and Director of the Khalifa Institute for Personalized Cancer Therapy at The University of Texas M.D. Anderson Cancer Center, Houston.

“We have here a roomful of thought leaders in cancer research and care—the best audience to identify our most pressing policy issues, and I look forward to hearing what you think are those with the highest priority—that have opportunities for action,” he said at the Institute of Medicine’s 2013 National Cancer Policy Summit, held recently in Washington, DC.

Basic and Translational Research

“Today’s cancer scientists must train replicas of themselves for the future,” said William G. Kaelin, Jr, MD, Professor of Medicine, Dana-Farber Cancer Institute, Boston. To that end, he suggested three critical needs: basic discovery in the public sector that complements private applied research, a sustainable model for scientific training and research funding, and exchange of information and reagents in the public and private sectors. In other words, he summarized, continue current efforts and make sure there’s money to keep it going.

Andrea Califano, PhD, Clyde and Helen Wu Professor of Chemical and Systems Biology, Columbia University, New York, talked about what he sees as the difference between traditional approaches to precision medicine and a systems biology approach. In the former, he said, predictions are based on statistical associations, whereas in the latter, predictions are based on a physical regulatory model. “Switching from one to the other requires significant change.”

He noted that there are now 500 phase III clinical trials underway in the United States. “This provides an untapped opportunity for precision medicine because it makes patient data broadly available to the research community; it allows blind, prospective prediction of responders vs nonresponders; and it is an evaluative tool when the study closes.”

He also believes that trials should be started earlier. “Patients may be too sick by the time they have access to experimental therapy.”

Spyro Mousses, PhD, Director of Pharmaceutical Genomics at TGen, Phoenix, noted that open biomedical knowledge and private patient data can be combined to form a systems oncology clearinghouse to form an evolving network of knowledge with links to drugs and patients’ genomic data, thus creating matches via evolving multiscalar models.

He posed three provocative questions. First, should personalized medicine and clinical drug development be regulated differently, or are they “flip sides of the same coin”?

Second, how do we refine policies that limit how genomic data are interpreted to inform clinical decisions?

Third, how do we reconcile evidence-based medicine when there is only one patient in a clinical trial (N=1)? Specifically, how do we incorporate mechanistic knowledge from genomic medicine to justify individual treatment decisions?

Diagnostics and Therapeutic Development

James H. Doroshow, MD, NCI Deputy Director for Clinical and Translational Research, Bethesda, Maryland, said that in order to optimize patient-centric models of cancer research, we need to change the preclinical paradigm to:

One with individual predictive therapeutic models using systems derived from molecularly characterized tumor biopsies or circulating DNA
Proof-of-mechanism trials, based on preclinical models that incorporate specific individualized data at treatment initiation as well as at disease progression
Collaboration that applies new models to drug development

Richard Pazdur, MD, Director of the U.S. Food and Drug Administration (FDA) Office of Hematology and Oncology Products, noted that because cancer drugs are more effective than ever, we need to rethink clinical trials. For example, instead of assuming that a randomized controlled trial is the best—or the only—way to demonstrate safety and efficacy, we need to rethink the way we do things and ask whether or not a randomized trial is needed or even ethical to conduct.

“Is a randomized trial appropriate at all when the control group is at a clear disadvantage at the outset and will likely cross over to the investigational arm to obtain the drug they believe is more effective from the start? Equipose may be lost from the onset,” he stated.

To expedite drug development when similar drugs are being developed for an indication, he suggested a study design in which several investigational drugs are compared at the same time to an already-approved common control. The investigational drugs would not necessarily be in competition with one another, and more than one could “win.”

“I also worry that investigational drug safety is rarely discussed and that there is a dearth of safety data we obtain from single-arm trials. We do not have comparative safety data when we rely on a single arm trial to determine safety and efficacy. We have to be more concerned about the harms these drugs are doing to patients, regardless of how effective they are and how life-threatening the disease,” said Dr. Pazdur.