Table of Contents
Clinical Trial Designs for First-line Hormonal Treatment of Metastatic Breast Cancer
Acknowledgements
Purpose
Hormone Drug Approval: Historical Perspective
Megestrol acetate (Megace)
Tamoxifen
Recent Approval Requirements for Hormonal Drugs
Approval Requirements for Hormonal Drugs
Historical Standards for Approval
Historical Standards for Approval
Recent Approvals
Hormonal Treatment of Metastatic Breast Cancer
Hormonal Drugs Approved in 2nd line Metastatic Breast Cancer
Hormonal Drugs Approved in 1st line Metastatic Breast Cancer
Toremifene: Fareston® 1st line Metastatic Breast Cancer
Non-inferiority Trial Design
Toremifene 1st line MBC Efficacy Results
Statistical Issues
Anastrozole: Arimidex® 1st line Metastatic Breast Cancer
Non-inferiority Trial Design
Anastrozole 1st line MBC Efficacy Results
Letrozole: Femara® 1st line Metastatic Breast Cancer
Letrozole 1st line MBC Efficacy Results
Recent Approvals
Issues to consider: TTP
Issues to consider: TTP
Issues to consider: Response Rate
Issues to consider: Response Rate
Issues to consider: Response Rate
Issues to consider: Response Rate
Additional Concerns: Choice of endpoint
Additional Concerns: Choice of endpoint
Additional concerns: Non-inferiority trial designs
Additional concerns: Non-inferiority trial designs
Additional concerns: Future applications
Statistical Considerations in Clinical Trial Designs for First-line Hormonal Treatment of Metastatic Breast Cancer
Outline
Active Control versus Drug “X”
Terminology
Assumptions
Non-inferiority Trial Design Considerations
Estimates of True Control Effect
Endpoint: Response Rate
Endpoint - Response Rate Sample Sizes - Point Estimate of Letrozole Effect Relative to Placebo
Endpoint - Response Rate Sample Sizes - Point Estimate of Letrozole Effect Relative to Tamoxifen
Endpoint - Response Rate Sample Sizes - Lower 95% C.L. of Letrozole Effect Relative to Placebo
Endpoint: Time to Progression
Endpoint - Time to Progression Sample Sizes - Point Estimate of Active Control Effect Relative to Tamoxifen
Endpoint - Time to Progression Sample Sizes - Lower 95% C.L. of Active Control Effect Relative to Tamoxifen
Endpoint - Time to Progression Sample Sizes - ? % Lower C.L. of Active Control Effect Relative to Tamoxifen, & preserving ? = 0.025
Summary: Endpoint Response Rate, 50% of Active Control Effect Retained
Summary: Endpoint Time-to-Progression, 50% of Active Control Effect Relative to Tamoxifen Retained
Sample Size For Superiority Trial With Tamoxifen As The Comparator
Perspective Issues
Issues for Discussion
Summary: Comparators
Summary: Endpoints
Questions to the Committee
PPT Slide
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