NDA 20-449 SE-011 Docetaxel

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NDA 20-449 SE-011Docetaxel

• FDA Review

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FDA Review Team

• Biostatistics
• Clara Chu, PhD.
• Gang Chen, PhD.
• Biopharmaceutics
• Safaa Ibrahim PhD
• Atiq Rahman, PhD.

• Project Manager
• Ann Staten, RD
• Medical
• Julie Beitz, MD

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Proposed Indication

• for the treatment of patients with locally
  advanced or metastatic NSCLC after failure of
  prior chemotherapy

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The Randomized, Controlled Trials

• TAX 317
• Docetaxel 100 mg (N 49)
• Best Supportive Care (N51)
  ?
• Docetaxel 75 mg(N55)
• Best Supportive Care (N49)

• TAX 320
• Docetaxel 100 mg(N125)
• Docetaxel 75 mg(N125)
• Vinorelbine OR Ifosfamide(N123)

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Trials Shared Features

• Eligibility/Exclusion Criteria
• prior platinum-based chemotherapy required in
  both studies
• prior taxane exposure excluded in TAX 317 only
• Primary Endpoint Survival
• Secondary Endpoints

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Major Efficacy Issues

• Pre-specified vs. Other Analyses
• Consistency across studies

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Survival - Prespecified Analyses
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Survival - Retrospective Analyses
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K-M Survival Curves - 75 mg vs. Control TAX 317
TAX 320
Tax
Tax
Control
BSC
S u r v I v I n g
S u r v I v I n g
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Rate of Survival at One Year - Retrospective
Analyses
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Historical Perspective

• Lack of phase 3 data in the second line setting
• First line rates of survival at one year are
  reported in the range of 18 - 43 for combination
  regimens (in randomized controlled trials)
• Gemcitabine Cisplatin 39
• Pactilaxel Cisplatin 36
• Vinorelbine Cisplatin 35

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Survival Summary of Review Issues

• A significant difference between arms was
  demonstrated in a pre-specified survival analysis
  in only one study (TAX317, pooled), in an updated
  analysis
• The analysis of overall survival at the 75 mg
  dose level favored docetaxel in a retrospective
  analysis of a single study (TAX317)
• Exploratory analyses of rates of one year
  survival favor docetaxel in both studies
• Rates of one year survival are comparable to
  those reported in the first line setting

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Clinical Benefit Parameters
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Safety
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Summary

• Safety ?
• QoL ?
• Survival ???