TAXOL

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TAXOL (paclitaxel) for Adjuvant Treatment of
Node Positive Breast Cancer
Oncologic Drugs Advisory Committee September 17,
1999
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TAXOL (paclitaxel) for Adjuvant Treatment of
Node Positive Breast CancerOncologic Drug
Advisory Committee INTRODUCTION

• David Tuck, M.D.
• Bristol-Myers Squibb Company
• Pharmaceutical Research Institute
• Wallingford, Connecticut

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PRESENTATIONS

• Introduction D. Tuck, M.D. BMS - PRI
• Adjuvant Chemotherapy L. Norton, M.D.For Breast
  Cancer MSKCC
• Pivotal Trial I.C. Henderson, M.D.Intergroup
  Study 0148 UCSF
• Concluding Remarks R. Canetta, M.D. BMS -
  PRI

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CALGB PARTICIPANTS

• Don Berry, Ph.D.Faculty Statistician CALGB
  Breast Committee
• M.D. Anderson Cancer Center - Houston, Texas
• Stephen George, Ph.D.
• Director CALGB Statistical Center
• Duke University - Durham, North Carolina
• I. Craig Henderson, M.D.Study Chair CALGB
• University of California at San Francisco,
  California
• Larry Norton, M.D.Chair CALGB Breast Committee
• Memorial Sloan-Kettering Cancer Center - New
  York, New York

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ACTIVITY IN BREAST CANCER

• TAXOL showed high response rates in Phase II
  trials in heavily pretreated patients, including
  anthracycline refractory patients
• One randomized trial (n471) led to FDA approval
  of TAXOL (175 mg/m2 over 3 hours) for the second
  line treatment of metastatic breast cancer in
  1994
• One randomized trial (n469) led to the approval
  of Herceptin, in combination with TAXOL (175
  mg/m2 over 3 hours), for the first line treatment
  of HER2 metastatic breast cancer in 1998

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TAXOL IN NODE POSITIVE BREAST CANCER PIVOTAL
TRIAL INT-0148 A Phase III Intergroup Study

• Trial Doxorubicin Dose Escalation, With or
  Without
• TAXOL, As Part Of the Cyclophosphamide/
  Doxorubicin Adjuvant Chemotherapy Regimen
  For Node Positive Breast Cancer
• Coordinating Group Cancer and Leukemia Group B
  (CALGB)
• Participating Groups Eastern Cooperative
  Oncology Group (ECOG)
• North Central Cancer Treatment Group
  (NCCTG)
• Southwest Oncology Group (SWOG)
• Enrollment 3,170 patients accrued from
• May 1, 1994 - April 15, 1997

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TAXOL IN NODE POSITIVE BREAST CANCER PIVOTAL
TRIAL INT-0148 A Phase III Intergroup Study

• The pivotal study is the largest randomized trial
  of chemotherapy in the adjuvant treatment of node
  positive breast cancer ever submitted to the FDA
• TAXOL (175 mg/m2 over 3 hours) given sequentially
  to standard chemotherapy demonstrates
  significant disease-free and overall survival
  advantages
• The safety profile of TAXOL in this setting is
  consistent with the large experience accumulated
  at this approved dose and schedule

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PROPOSED INDICATION

• TAXOL (paclitaxel) administered sequential to
  standard combination chemotherapy is
  indicated for the adjuvant treatment of
  node positive breast cancer

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