On Label and Off-Label Use of Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer

CMS evidence review | evidence_type=MEDCAC Meeting | record_type=medcac_meeting | document_id=56 | meeting_date=2010-11-17

The Centers for Medicare and Medicaid Services (CMS) has called this meeting to consider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer. As described on the FDA website at http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm213559.htm, “PROVENGE® (Sipuleucel T, APC8015) is an autologous cellular immunotherapy product consisting of peripheral blood mononuclear cells (PBMCs) obtained from patients by leukapheresis and activated in vitro with a recombinant fusion protein (prostatic acid phosphatase fused with GM-CSF). FDA will require the sponsor to complete a post marketing study to evaluate the risk of stroke in patients who receive sipuleucel-T.” Provenge® has FDA approved labeling for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

Actions Taken: August 31, 2010 Announced meeting. Those interested can register at: http://www.cms.gov/apps/events/event.asp?id=610&Kw=&Mh=NoMonth&cboOrder=date&Yr=NoYear&type=2 September 24, 2010 Posted FR Notice and questions to panel. October 26, 2010 We will be broadcasting the meeting via Webinar. You must register for the Webinar portion of the meeting at https://webinar.cms.hhs.gov/txmetaprostatemedcac1117/event/registration.html November 10, 2010 Posted technology assessment . November 15, 2010 Posted agenda , roster and speaker list . November 18, 2010 Posted scoresheet [PDF, 35KB] from meeting. December 27, 2010 Posted minutes [PDF, 129KB] and transcript [PDF, 339KB] from meeting. Agenda: Federal Register Notice Agenda Medicare Evidence Development & Coverage Advisory Committee November 17, 2010 7:30 AM - 4:30 PM CMS Auditorium Clifford Goodman, PhD, Chair Saty Satya-Murti, MD, Vice Chair James Rollins, MD, Division Director, Division of Items and Devices, Coverage and Analysis Group Maria Ellis, Executive Secretary 7:30 - 8:00 AM Registration 8:00 - 8:15 AM Opening Remarks— Maria Ellis/James Rollins, MD/Clifford Goodman, PhD 8:15 - 8:25 AM CMS Presentation of Voting Questions - Lori Paserchia, MD 8:25 - 8:50 AM James L. Gulley, MD, PhD, FACP, Director, Clinical Trials Group, Laboratory of Tumor, Immunology and Biology, Principal Investigator, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health 8:50 - 9:50 AM TA Presentation: David Mark, MD, MPH, Senior Scientist, Blue Cross Blue Shield Association, Technology Evaluation Center 9:50 - 10:05 AM BREAK 10:05 - 10:50 AM Scheduled Public Comments (Refer to Speaker List) Public attendees, who have contacted the executive secretary prior to the meeting, will address the panel and present information relevant to the agenda. Speakers are asked to state whether or not they have any financial involvement with manufacturers of any products being discussed or with their competitors and who funded their travel to this meeting. 10:50 - 11:05 AM Open Public Comments Public Attendees who wish to address the panel will be given that opportunity 11:05 - 12:00 PM Questions to Presenters 12:00 - 1:00 PM LUNCH (on your own) 1:00 - 2:00 PM Initial Open Panel Discussion: Dr. Goodman 2:00 - 3:00 PM Formal Remarks and Voting Questions The Chairperson will ask each panel member to state his or her position on the voting questions 3:00 - 4:00 PM Final Open Panel Discussion: Dr. Goodman 4:00 - 4:30 PM Closing Remarks/Adjournment: Dr. Rollins & Dr. Goodman Associated Nca: Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer (CAG-00422N) Issue: The Centers for Medicare and Medicaid Services (CMS) has called this meeting to consider the currently available evidence regarding the impact of labeled and unlabeled use of autologous cellular immunotherapy treatment on health outcomes of patients with metastatic prostate cancer. As described on the FDA website at http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm213559.htm, “PROVENGE® (Sipuleucel T, APC8015) is an autologous cellular immunotherapy product consisting of peripheral blood mononuclear cells (PBMCs) obtained from patients by leukapheresis and activated in vitro with a recombinant fusion protein (prostatic acid phosphatase fused with GM-CSF). FDA will require the sponsor to complete a post marketing study to evaluate the risk of stroke in patients who receive sipuleucel-T.” Provenge® has FDA approved labeling for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Minutes: Download meeting minutes [PDF, 113KB]. Other Material: Transcript 1 Directions to CMS Panel Voting Questions: MEDCAC –November 17, 2010 DRAFT QUESTIONS Autologous Cellular Immunotherapy Treatment of Metastatic Prostate Cancer FDA Label - PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Voting Questions For all voting questions, the health outcomes of interest are: overall survival, control of disease-related symptoms, and the avoidance or minimization of the burdens to patients associated with anticancer therapy. The comparator is the management that the patient would otherwise have received. For the voting questions, use the following scale identifying level of confidence - with 1 being the lowest or no confidence and 5 representing a high level of confidence. 1 — 2 — 3 — 4 — 5 Low Intermediate High Confidence Confidence Confidence How confident are you that there is adequate evidence to determine whether or not the use of autologous cellular immunotherapy treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer significantly improves: Overall survival? 1 — 2 — 3 — 4 — 5 Control of disease-related symptoms? 1 — 2 — 3 — 4 — 5 Avoidance or minimization of the burdens associated with anticancer therapy while maintaining overall survival and control of disease-related symptoms? 1 — 2 — 3 — 4 — 5 Note: Questions 2 -6 should be addressed only for those outcomes under question 1 where the panel is confident that there is at least intermediate confidence (mean vote of 2.5) that there is adequate evidence to make the determination of improvement. How confident are you that there is adequate evidence to conclude that autologous cellular immunotherapy treatment significantly improves overall survival in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer? 1 — 2 — 3 — 4 — 5 How confident are you that there is adequate evidence to conclude that autologous cellular immunotherapy treatment significantly improves control of disease-related symptoms in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer? 1 — 2 — 3 — 4 — 5 How confident are you that there is adequate evidence to conclude that autologous cellular immunotherapy treatment significantly improves the avoidance of the treatment burdens (e.g., access, delivery, or side-effects) associated with anticancer therapy in patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer? 1 — 2 — 3 — 4 — 5 How confident are you that these conclusions are generalizable to unlabeled use in: Patients whose prostate cancer has not metastasized? 1 — 2 — 3 — 4 — 5 Patients who have metastatic, castrate resistant disease and symptoms more severe than minimally symptomatic? 1 — 2 — 3 — 4 — 5 Patients who have metastatic prostate cancer but who have not failed hormonal therapy? 1 — 2 — 3 — 4 — 5 How confident are you that these conclusions are generalizable to: Community based settings? 1 — 2 — 3 — 4 — 5 Patients belonging to demographic groups that may have been under-represented in the enrolled clinical trial populations? 1 — 2 — 3 — 4 — 5 Discussion Questions Do you believe that there is adequate evidence to identify patients who are more likely or less likely to respond favorably to autologous cellular immunotherapy treatment based on pretreatment evaluation of any of the following factors? Site(s) or number of metastasis(es) as detected by imaging studies Gleason score Alkaline phosphatase (U/L) Hemoglobin (g/dL) Serum LDH (U/L) Serum PSA (ng/mL) Pain associated with metastatic, castrate-resistant prostate cancer Other What significant evidence gaps exist regarding the health outcomes attributable to autologous cellular immunotherapy treatment? For the FDA-labeled indication? For off-label uses? What clinical study designs would adequately address any evidence gaps? Download scoresheet [PDF, 35KB] Roster: Clifford Goodman, PhD CHAIR Senior Vice President The Lewin Group Saty Satya-Murti, MD, FAAN VICE CHAIR Health Policy Consultant Helen Darling, MA National Business Group on Health Roger Dmochowski, MD Department of Urology Vanderbilt University Dale Fuller, MD Radiation Oncologist Texas Oncology, PA Karl Matuszewski, MS, PharmD Vice President, Editor-in-Chief Elsevier/Gold Standard David M. Mintzer, MD Chief Section of Hematology and Medical Oncology Medical Director Pain and Supportive Care Services Pennsylvania Hospital Clinical Associate Professor of Medicine University of Pennsylvania Pearl Moore, RN, MN, FAAN Adjunct Assistant Professor University of Pittsburgh School of Nursing Louis Potters, MD, FACR Chairman Department of Radiation Medicine North Shore – Long Island Jewish Health Kevin Schulman, MD, MBA Professor of Medicine Duke University School of Medicine Robert L. Steinbrook, MD Adjunct Associate Professor of Medicine Community and Family Medicine Dartmouth Medical School Industry Representative G. Gregory Raab, PhD Health Policy Consultant Raab Associates Guest Panel Members Ravi A. Madan, MD Assistant Clinical Investigator Laboratory of Tumor Immunology and Biology and Medical Oncology Branch National Cancer Institute Nation Institute of Health Mitchell Howard Sokoloff, MD, FACS Professor of Surgery and Chief of Urology Division of Urology Department of Surgery University of Arizona College of Medicine Invited Guest Speaker James L. Gulley, MD, PhD, FACP Director Clinical Trials Group, Laboratory of Tumor Immunology and Biology Principal Investigator Medical Oncology Branch Center for Cancer Research National Cancer Institute National Institutes of Health CMS Liaison James Rollins, MD Division Director Division of Items and Devices Coverage and Analysis Group Executive Secretary Maria Ellis Coverage and Analysis Group Speaker List: Medicare Evidence Development & Coverage Advisory Committee November 17, 2010 SPEAKER LIST *5 MINUTES PER SPEAKER* Paul F. Schellhammer, MD, Professor of Urology, Eastern Virginia Medical School - Representing: American Urological Association Brad Loncar, Lenexa, Kansas James J. Kiefert, MD, Board Chairman Emeritus, Us TOO, International Daniel P. Petrylak, MD, Professor of Medicine, Columbia University Medical Center Saurabh Aggarwal, PhD, Healthcare Consultant, Bethesda, Maryland Mark Scholz, MD, Medical Director, Prostate Oncology Specialists, Inc., Marina Del Rey, California Thair Phillips, President, Retire Safe Mark W. Frohlich, MD, Chief Medical Officer, Dendreon Corporation Philip Kantoff, MD , Professor of Medicine, Harvard Medical School, Director, Genitourinary Oncology, Chief Clinical Research Officer and Chief Division of Solid Tumor Oncology, Dana-Farber Cancer Institute