Clinical Trial Designs for First-line Hormonal Treatment of Metastatic Breast Cancer

9/25/01


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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

Author: FDA.CDER