eastern cooperative oncology group ACRIN Annual Meeting OVERVIEW OF ECOG Robert L. Comis, M.D. Chair Eastern Cooperative Oncology Group September 22, 2011

eastern cooperative oncology group ECOG Constitution Mission Statement The Eastern Cooperative Oncology Group (ECOG) is a multidisciplinary organization devoted to the prevention, treatment and study of neoplastic disease that will eventually lead to the control and cure of cancer. 1

eastern cooperative oncology group Organizational Structure GroupChair Vice Chair Group Statistician Group Chair’s Office Operations Office Research & Education Foundation Statistical Center Administrative Committees Principal Investigators Scientific Committees Academic Members CCOP Members Affiliates Academic Members Other Scientific Committees Disease Committees 2

eastern cooperative oncology group Scientific and Administrative Senior Leadership  Chair – Dr. Robert Comis  Vice Chair – Dr. Peter O’Dwyer  Group Statistician – Dr. Robert Gray  Executive Officer – Dr. Bruce Giantonio  Associate Chair – Dr. Joseph Sparano  Coordinating Center Co-Directors – Ms. Jean MacDonald and Ms. Mary Steele  Director of Operations – Ms. Donna Marinucci  Regulatory Officer – Dr. Robert Catalano 3

eastern cooperative oncology group Main Academic Member Institutions U10 Funded  Albert Einstein Cancer Center  Beth Israel Deaconess Medical Center  Cancer Institute of New Jersey  Case Western-MetroHealth Medical Center  Fox Chase Cancer Center  Indiana University Medical Center  Johns Hopkins University  Mayo Clinic  Northwestern University  University of Pennsylvania  University of Pittsburgh  University of Wisconsin  Vanderbilt University Non-U10 Main Members  Emory University School of Medicine  Instituto de Enfermedades Neoplasicas (Lima, Peru)  Ireland Cooperative Oncology Research Group  New York University Medical Center  Stanford University  The Penn State Cancer Institute  Tufts Medical Center  University of Alabama  University of Miami 4

eastern cooperative oncology group Primary CCOPs  Colorado Cancer Research Program CCOP  Cook County MBCCOP*  Evanston Hospital CCOP  Kalamazoo CCOP  Main Line Health CCOP  Marshfield Clinic CCOP  Medical College of Georgia MBCCOP*  Meharry Medical College MBCCOP*  Metro-Minnesota CCOP  Ochsner CCOP  Oklahoma CCOP  San Juan MBCCOP*  SUNY Downstate MBCCOP*  St Vincent Hospital Regional Center CCOP 5 *Minority Based CCOP

eastern cooperative oncology group Administrative and Scientific Organizational Structure Administrative Committees - Audit - CRA - Data Monitoring - Executive Review - Nominating - Oncology Nursing - Patient Representative - Pharmacy - Radiation Oncology - Surgery Scientific Committees Disease Committees Other Scientific Committees - Breast- Laboratory Science - Gastrointestinal and Pathology - Genitourinary- Developmental Therapeutics - Head and Neck- Pathology Coordinating - Leukemia Office/Reference Laboratory - Lymphoma- Central Immunologic - Melanoma Monitoring Laboratory - Myeloma- Leukemia Laboratory - Thoracic- Cytogenetics DCP Funded Committees: - Patient Outcomes, Survivorship and Underserved - Prevention - Symptom Management 6

eastern cooperative oncology group Accrual Registrations to Therapeutic Studies (Projected)(Average)

eastern cooperative oncology group CTSU Participation ECOG Participation in CTSU Menu Studies ECOG studies on the CTSU menu 31 CTSU studies “endorsed” by ECOG 44 CTSU patients accrued to ECOG studies 11,417 ECOG patients accrued to CTSU studies 6,618 ECOG patients accrued to other intergroup studies1,714 8

eastern cooperative oncology group Major Accomplishments  Six studies led to new standard of care and FDA indications  Bevacizumab in metastatic colon (E3200), lung (E4599), breast (E2100)  Rituximab in indolent (E1496) and aggressive lymphoma (E4494)  Thalidomide in multiple myeloma (E1A00)  Two phase III adjuvant trials:  E5103 – bevacizumab + chemotherapy in HER2- negative breast cancer  E1505 – bevacizumab + chemotherapy in stage IB – IIIA NSCLC 9

eastern cooperative oncology group Major Accomplishments  Head and Neck cancer: defined prognostic and predictive roles of p53 mutations and HPV+  AML: established superiority of high dose daunorubicin induction  Adult ALL: defined new adverse cytogenetic parameters  Breast cancer: described VEGF SNPs related to response and toxicity; and potential new therapeutic targets (eg, GRB-7)  Multiple Myeloma: established superiority of low dose dexamethasone plus lenalidomide in induction therapy 10

eastern cooperative oncology group Publication Record ( ) JCO93Blood18 NEJM9 11

eastern cooperative oncology group Peer-Review Funding:  Laboratory Science and Pathology Committee (LSPC)  Reviews, comments on and approves all ECOG related grant studies prior to submission  22 R01 and R21 proposals were reviewed and approved by LSPC  50% of RO1 and R21 submissions were funded by NIH 12

eastern cooperative oncology group Peer-Review Funding: NIH Total29 R0121*/29 (72%) *8/14 correlative research grants R21/Other8/29 (28%) Other Breast Cancer Research Foundation2 Susan B. Komen Foundation1 American Cancer Society1 Lymphoma Research Foundation1 Leukemia and Lymphoma Society2 13

eastern cooperative oncology group Major Accomplishments  Key components of our Translational Science effort  Laboratory Science and Pathology Committee  PCO-RL and other core laboratories  Developmental Therapeutics Committee  Pharmacogenetics subcommittee studies  Leukemia Laboratory Committee and Leukemia Translational Research Laboratory  Translational Science Team  IT infrastructure 15 14

eastern cooperative oncology group Major Accomplishments  Established scientific infrastructure to perform large-scale biomarker driven studies  Launched two large marker-driven phase III studies  E5202 – stage II colon cancer (MSI; 18q LOH)  TAILORx (PACCT-1) – node negative breast cancer (Oncotype-DX) 16 15

eastern cooperative oncology group E5202 Trial Schema Low-Risk Patients MSS or MSI-L with retention of 18q alleles MSI-H Arm A: mFOLFOX6 q2w × 12 Arm B: mFOLFOX6 + bevacizumab* q2w × 12 Arm C: Observation only High-Risk Patients MSS/18q LOH or MSI-L/18q LOH are RANDOMIZED MSI-L = low-level microsatellite instability MSI-H = high-level microsatellite instability *bevacizumab continued for an additional 6 months Stratify: Disease stage (IIA or IIB) Microsatellite stability (stable vs MSI) 18q LOH 16

eastern cooperative oncology group Integral Biomarker Specimen Flow—E5202 Site registers patient, ships 2 blocks (1 tumor, 1 normal) PCO-RL * Laboratory QC and Processing MDACC* tests for 18qLOH, MSI Surgery ECOG Rando Site registers patient to Treatment 60 days max60 days max60 days max60 days max Fax results - avg 4 working days 5 working days * CAP-accredited lab for CLIA-88 compliance 17

eastern cooperative oncology group General Themes for the Future  Study “targeted” therapies with the ultimate goal of developing new potentially curative strategies  Define new predictive and prognostic factors which lead to hypothesis driven clinical trials  Continue to develop both laboratory-based and IT infrastructure  Build upon new data from existing pivotal studies undergoing completion and analysis 19