FACILITATING
COLLABORATIONS TO
DEVELOP COMBINATION
INVESTIGATIONAL
CANCER THERAPIES
WORKSHOP SUMMARY
Margie Patlak, Erin Balogh, and Sharyl J. Nass, Rapporteurs
National Cancer Policy Forum
Board on Health Care Services
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington D.C.
www.nap.edu
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.
This study was supported by Contract Nos. HHSN261200900003C and 200-2005-13434 TO #1 between the National Academy of Sciences and the National Cancer Institute and the Centers for Disease Control and Prevention, respectively. In addition, the National Cancer Policy Forum is also supported by the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, the Association of American Cancer Institutes, Bristol-Myers Squibb, C-Change, the CEO Roundtable on Cancer, Novartis Oncology, and the Oncology Nursing Society. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
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Suggested citation: IOM (Institute of Medicine). 2012. Facilitating collaborations to develop combination investigational cancer therapies: Workshop summary. Washington, DC: The National Academies Press.
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
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WORKSHOP PLANNING COMMITTEE1
JOHN HOHNEKER (Chair), Senior Vice President and Head, Global Development, Integrated Hospital Care, Novartis Pharma AG, Basel, Switzerland
RENZO CANETTA, Vice President, Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT
MICHAELE CHAMBLEE CHRISTIAN, Retired, Washington, DC
ROY S. HERBST, Chief of Medical Oncology, Yale Cancer Center, New Haven, CT
PATRICIA LoRUSSO, Professor of Medicine and Director, Center for Experimental Therapeutics, Barbara Ann Karmanos Cancer Institute, Detroit, MI
FRANK McCORMICK, Director, University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, and Associate Dean, UCSF School of Medicine
RICHARD PAZDUR, Director, Office of Oncology Drug Products, Food and Drug Administration, Silver Spring, MD
PHILIP D. PORTER, Partner, Hogan Lovells, McLean, VA
ELLEN SIGAL, Chairperson and Founder, Friends of Cancer Research, Washington, DC
JOHN A. WAGNER, Vice President, Clinical Pharmacology, Merck and Company, Inc., Rahway, NJ
JAMES A. ZWIEBEL, Chief, Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD
Project Staff
ERIN BALOGH, Study Director
MICHAEL PARK, Senior Program Assistant
SHARYL J. NASS, Director, National Cancer Policy Forum
ROGER HERDMAN, Director, Board on Health Care Services
1 The Institute of Medicine planning committee was solely responsible for organizing the meeting, identifying topics, and choosing speakers. The responsibility for the published summary rests with the rapporteurs and the institution.
NATIONAL CANCER POLICY FORUM1
JOHN MENDELSOHN (Chair), President, MD Anderson Cancer Center, Houston, TX
PATRICIA A. GANZ (Vice Chair), Professor, University of California at Los Angeles (UCLA) School of Medicine & Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, CA
AMY ABERNETHY, Associate Professor of Medicine, Duke University School of Medicine, and Director, Duke Cancer Care Research Program, Durham, NC
FRED APPELBAUM, Director, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
PETER B. BACH, Attending Physician, Memorial Sloan-Kettering Cancer Center, New York
EDWARD BENZ, JR., President, Dana-Farber Cancer Institute and Director, Harvard Cancer Center, Harvard School of Medicine, Boston, MA
MONICA BERTAGNOLLI, Professor of Surgery, Harvard University Medical School, Boston, MA
OTIS W. BRAWLEY, Chief Medical Officer, American Cancer Society, Atlanta, GA
MICHAEL A. CALIGIURI, Director, Ohio State Comprehensive Cancer Center, Columbus, OH, and President, Association of American Cancer Institutes
RENZO CANETTA, Vice President, Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, CT
MICHAELE CHAMBLEE CHRISTIAN, Retired, Washington, DC
WILLIAM DALTON, President, CEO, and Center Director, Moffitt Cancer Center, Tampa, FL, and Chair, AACR Committee on Science Policy and Legislative Affairs
WENDY DEMARK-WAHNEFRIED, Associate Director for Cancer Prevention and Control, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL
ROBERT ERWIN, President, Marti Nelson Cancer Foundation, Davis, CA
ROY S. HERBST, Chief of Medical Oncology, Yale Cancer Center, New Haven, CT
1 Institute of Medicine forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published meeting summary rests with the rapporteurs and the institution.
JOHN HOHNEKER, Senior Vice President and Head, Global Development, Integrated Hospital Care, Novartis Pharma AG, Basel, Switzerland
THOMAS J. KEAN, President and Chief Executive Officer, C-Change, Washington, DC
DOUGLAS R. LOWY, Deputy Director, National Cancer Institute, Bethesda, MD
DANIEL R. MASYS, Affiliate Professor, Biomedical and Health Informatics, University of Washington School of Medicine, Seattle, WA
MARTIN J. MURPHY, Chief Executive Officer, CEO Roundtable on Cancer, Durham, NC
BRENDA NEVIDJON, Clinical Professor and Specialty Director, Nursing & Healthcare Leadership, Duke University School of Nursing, Durham, NC, and Past President, Oncology Nursing Society
STEVEN PIANTADOSI, Director, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
LISA C. RICHARDSON, Associate Director for Science, Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA
YA-CHEN TINA SHIH, Director, Program in the Economics of Cancer, University of Chicago, Chicago, IL
ELLEN SIGAL, Chairperson and Founder, Friends of Cancer Research, Washington, DC
JOHN A. WAGNER, Vice President, Clinical Pharmacology, Merck and Company, Inc., Rahway, NJ
RALPH R. WEICHSELBAUM, Chair, Radiation and Cellular Oncology, and Director, Ludwig Center for Metastasis Research, The University of Chicago Medical Center, Chicago, IL
JANET WOODCOCK, Director, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD
National Cancer Policy Forum Staff
SHARYL J. NASS, Director, National Cancer Policy Forum
LAURA LEVIT, Program Officer
CHRISTINE MICHEEL, Program Officer
ERIN BALOGH, Associate Program Officer
MICHAEL PARK, Senior Program Assistant
PATRICK BURKE, Financial Associate
SHARON B. MURPHY, Scholar in Residence
ROGER HERDMAN, Director, Board on Health Care Services
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Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Ramzi Dagher, Vice President, Worldwide Regulatory Strategy and Regulatory Head, Oncology Business Unit, Pfizer, Inc., New London, CT
Beloo Mirakhur, Senior Director, R&D/Medical Affairs, Oncology N.A., GlaxoSmithKline, Collegeville, PA
Jane Perlmutter, Founder, Gemini Group, Ann Arbor, MI
Jeffrey Sosman, Professor of Medicine and Director, Melanoma & Tumor Immunotherapy Program, Vanderbilt-Ingram Cancer Center, Nashville, TN
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the final draft of this report. The review of this report was overseen by Melvin
Worth. Appointed by the Institute of Medicine, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
Contents
2 WHY COMBINATIONS AND COLLABORATIONS ARE NECESSARY
3 SCIENTIFIC CHALLENGES IN DEVELOPING INVESTIGATIONAL COMBINATION THERAPIES
Improving Preclinical Development of Investigational Combination Therapies
Prioritizing Combinations to Test
Building on the Basic Knowledge Base
Improving Clinical Trials for Combination Therapies
4 OVERCOMING CULTURAL CHALLENGES TO COLLABORATIONS
Showing the Contribution of Each Drug in a Combination
Effect of Combined Toxicity on Single-Agent Approval
Labeling Combination Therapies
Coordination of Diagnostic and Therapeutic Regulation
FDA Versus European Regulation
8 CODEVELOPMENT OF THERAPIES FOR HIV AS A MODEL
The Importance of Surrogate Markers
Vaccines in Combination Therapies
The Key Role of Patient Advocates
9 EXAMPLES OF COLLABORATIONS RELEVANT TO CANCER
APPENDIXES
Table, Box, and Figures
TABLE
4-1 Rankings of Immunotherapy Agents with High Potential for Use in Treating Cancer
BOX
FIGURES
2-1 Growth factor receptor signal transduction pathways
2-3 Clonal evolution of human neoplasia
3-2 Design features of an I-SPY-like trial
8-1 Instantaneous inhibitory potential (IIP) of antiretroviral drugs
