Concluding Remarks and Risk/Benefit Summary

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Concluding Remarks and Risk/Benefit Summary

• Mace L. Rothenberg, MD
• Professor of Medicine
• Vanderbilt Ingram Cancer Center

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Historical Context Therapeutic Advances in
Advanced Pancreatic Cancer

• 1995 Gemcitabine presented to ODAC
• Small but significant improvement in survival
• Low objective response rate
• Higher rates of Grade 3-4 myelosuppression, ?
  LFTs, nausea and vomiting
• 1996 Gemcitabine approved by FDA for advanced
  pancreatic cancer

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Historical Context Therapeutic Advances in
Advanced Pancreatic Cancer

• 1996 2005
• 2 Phase III trials of new drug vs gemcitabine
• None demonstrated a survival benefit
• 8 Phase III trials of new drug gemcitabine vs
  gemcitabine alone or with placebo
• None demonstrated a survival benefit
• Clearly, improving outcomes in advanced
  pancreatic cancer has been more difficult than
  anticipated

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Tarceva and Advanced Cancers

• Pancreatic cancer is a fatal disease
• Overall survival is the shortest of any solid
  tumor
• In other Phase III trials, the addition of a
  second agent to gemcitabine has added toxicity
  without an improvement in survival
• Tarceva was approved by the FDA in 2004 after
  demonstrating improvement in overall survival in
  patients with recurrent NSCLC
• Clinical experience and safety profile for
  Tarceva in greater than 18,000 patients

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What is Under Consideration sNDA

• The application under consideration today is a
  supplemental NDA, a mechanism created by the FDA
  to encourage sponsors to submit significant
  clinical trial data and thereby promote
  concordance between labeled indications and
  emerging clinical use of the drug.
• FDA Guidance for Industry If a product already
  has been shown to be safe and effective in the
  treatment of patients with a given type of
  cancer, a single, adequate and well-controlled,
  multicenter study demonstrating acceptable safety
  and effectiveness in another form of cancer that
  is known to have a generally similar pattern of
  responsiveness to chemotherapy may support
  labeling for that additional form of cancer.

FDA Guidance For Industry FDA Approval of New
Cancer Treatment Uses for Marketed Drug and
Biological Products (December 1998)
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NCIC CTG PA.3 is a Well-Designed, High-Quality
Study

• Randomized, double-blind, placebo-controlledPhase
  III trial
• Conducted independently by a North American
  Cooperative Group with support from OSI
• Primary endpoint, improvement in overallsurvival
  achieved
• Therapeutic benefit conferred that is both
  statistically significant and clinically
  meaningful
• 23 increase in overall survival
• 30 increase in progression-free survival
• A point estimate, such as median survival, does
  not accurately capture this benefit

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NCIC CTG PA.3 is a Well-Designed, High-Quality
Study

• Benefit associated with modest or infrequent
  toxicities
• Primarily rash and diarrhea
• Rare episodes of ILD-like events
• No worsening of global quality of life
• Magnitude of toxicity is substantially less than
  what has been observed when other cytotoxic
  agents have been added to gemcitabine
• Tarceva is an oral, self-administered drug that
  does not place a burden on outpatient resource
  utilization or inconvenience the patient

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Implications of Study PA.3 for Patients with
Advanced Pancreatic Cancer

• PA.3 the first trial in 10 years to demonstrate
  significant improvement in survival in patients
  with advanced pancreatic cancer
• The type and magnitude of benefits far outweigh
  the risk of toxicities
• Tarceva and gemcitabine an important treatment
  option for patients and physicians who want a
  more aggressive, more effective treatment for
  advanced pancreatic cancer
• They should have that choice!