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Prof. Jean-Marc Nabholtz, MD, MSc Chairman

Prof. Jean-Marc Nabholtz, MD, MSc Chairman. Breast Cancer. Worldwide (2000): > 800,000 new cases 350,000 deaths Death rates: From 1930 until 1990: stable 1990’s: slight decrease Screening Adjuvant therapy, real but Modest. Cancer Therapy Development. NEW SINGLE AGENT. Addition to

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Prof. Jean-Marc Nabholtz, MD, MSc Chairman

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  1. Prof. Jean-Marc Nabholtz, MD, MSc Chairman

  2. Breast Cancer • Worldwide (2000): • > 800,000 new cases • 350,000 deaths • Death rates: • From 1930 until 1990: stable • 1990’s: slight decrease • Screening • Adjuvant therapy, real but Modest

  3. Cancer Therapy Development NEW SINGLE AGENT Addition to Prior standard MBC ADJUVANT Nabholtz, May, 2001

  4. BREAST CANCERNew Drug Development • Number factor: • Exponential increase of number of new drugs • 1970s and 80s: one digit number • 1990s: two digit number • 2000s: explosion of biotech development • Relatively fixed number of patients and clinical researchers available for clinical research

  5. BREAST CANCERNew Drug Development • Time factor: • Long lead time between Phase I and Adjuvant Phase III: 20 years for doxorubicin • Classical groups • Activation time: 18 months average • Accrual time: 2 to 5 years • Follow-up time • Preliminary results at 3 years • Final results at 5 to 10 years.

  6. BREAST CANCERNew Drug Development Key factors for the future Patient Access Quality of Concepts/Speed Quality of Data

  7. BREAST CANCERNew Drug Development • Need to adapt to the challenge: • Quality: Academic control with global strategies of development • Speed: • Globalization of processes: Worldwide network of investigators • Adaptation to the needs (Virtual): • Access to patients where they are • Use of modern means of communication

  8. Breast Cancer New Drug DevelopmentAcademic Global Virtual Concept BCIRG First Academic Global Virtual Intergroup

  9. BCIRG PRIORITY MANDATES • Patients • Safety • Improving care • Science • Studies of new Drugs • Vehicule: Global Strategy of Development • Rationales built from evidence • Scientific Independence • Academic Collaboration

  10. BCIRG Investigators

  11. BCIRG Offices Edmonton Paris Los Angeles

  12. BCIRG Support Investigators • The Academic Group: • Group Development • New Therapy Identification • Global Strategy Development • Academic Stimulation • Statistics • Communications • Academic support • The Operations Group: • State of the Art • CRAs and Management • Data Entry and Management • Regulatory/Safety • Trial Implementation • Information Technology • Administration

  13. BCIRG Investigator Organization Study Chairs Leaders of the studies Core Centers Dedicated to BCIRG studies, launch all phases of studies Investigators 1500 investigators from 850 centers comprise our cooperative group

  14. BCIRG Investigator Organization BCIRG … = participating center = participating regional/national cooperative group = non-participating centers or group

  15. BCIRG Scientific Advisory Board Overall Scientific Advisory Board Evaluation of New Compounds Choice Steering committees: Hormonotherapy, Biologic modifiers, Chemotherapy Global Strategy of Development

  16. BCIRG Strategy Implementation Global Strategy of Development Advisory Board Review BCIRG Academic Team BCIRG Operations Team Implementation: Phases I to III

  17. Development of Chemotherapy Breast Cancer 1970s • Before anthracyclines • CMF, CMFVP • With anthracyclines • Combinations: AC, FAC, AVCMF, FEC, CEF • Sequence and Alternating (Milan A & B) • Dose intensity,dose density, HDCT • Taxanes (Paclitaxel/Docetaxel) • Sequential: A T C or AC T • Combinations: TA, TAC • Biologic Modifiers (Herceptin) • Integration in chemotherapy strategies 1980s 1990s 2000s

  18. BCIRG: Genesis and Proof of Concept • Development of Taxanes • Taxol with BMS: Registration trial 1993-1996 • Taxotere with RPR/Aventis • 7 Pivotal Phase III trials • MBC • Tax 304: Txt vs. MV (registration trial) • Tax 306: AT vs. AC (registration trial) • Tax 307: TAC vs. FAC (registration support) • Adjuvant • BCIRG 001/Tax 316: TAC vs. FAC (registration trial) • BCIRG 002/Tax 321: TAC vs. TAC & HDCT • BCIRG 005: ACT vs. TAC • BCIRG 006: ACT vs. ACTH vs. TCH

  19. Hormonetherapy • Arimedex: Registration trial vs Tamoxifen 1st line Metastatic with AstraZeneca • SCH 57050 vs anastrazole metastatic breast cancer relapsing • Pivotal registration trial • Complete

  20. Development of MPO with Searle/Monsanto • Concept: Improve AT/TAC toxicity profile (Febrile Neutropenia) • Phase III MPO vs G-CSF after TAC chemotherapy (Registration Trial)

  21. BCIRG: Current Focus (I) 2nd Generation Adjuvant Development of Taxotere/ 1st Generation Adjuvant Development of Herceptin • Adjuvant • BCIRG 005: ACT vs. TAC • BCIRG 006: ACT vs. ACTH vs. TCH • Metastatic • Phase II Pilots of TCH (BCIRG 101/102) • BCIRG 007: TH vs. TCH (Roche Genentech)

  22. BCIRG: Current Focus (II) • Development of Other promising new agents : • new biologic modifiers : • EGFR-TKI Inhibitors (Iressa-AstraZeneca, OSI-774-Genentech…) Iressa Global strategy of development • Anti-Angiogenic Molecules… • Chemotherapy (Xeloda): Registration trial of Xeloda in adjuvant setting • Under discussion • Node negative High Risk • Elderly

  23. Evolution • BCIRG is the Breast Cancer division of CIRG (Cancer International Research Group) • Present evaluation of potential other divisions • Disease sites eg. LCIRG, GICIRG… • Mechanistic groups: Kinase Inhibitors IRG …others?... • Integration of activities in Global Translational Processes. • with UCLA/JCCC and other Universities • Development of Translational Tools (Cancer International Tumor Bank)….

  24. Global Translational Processes

  25. Multistep Process: 7 major steps • 1. Identification of Gene abnormalities • 2. Determination of relevance in human cancers • 3. Pathway Identification • 4. Identification of therapeutic interventions • 5. Identifications of patients sub-populations with given abnormality / Tests • 6. Identification of predictive factors / Tests • 7. Pivotal clinical development

  26. Translationnal Multistep Process(7 of 7) • Pivotal Global Clinical Development • Acces to multiple targeted subpopulations in a timely fashion for proof of concept in humans CIRG First Academic Global Translational Intergroup

  27. Meeting the Challenges • Phenomenal acceleration of new compounds • Emergence of targeted therapies in subpopulations • Concept of biology based individualized therapy • Need to define new models of development and define new translational strategies • Patient Access • Overall stable number of patients • Targeted therapies: Need to study subpopulations • Need for new processes for developing new drugs

  28. Summary: Science is our guide • BCIRG and CIRGwere created to meet that need • The concept has been proven to work • Integrated Translational approach • Academic Global Translational collaboration

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