# Presentation: 729496

## TAXOL® (paclitaxel) for Adjuvant Treatment of Node Positive Breast Cancer

- Oncologic Drugs Advisory Committee
- September 17, 1999

## TAXOL® (paclitaxel) for Adjuvant Treatment of Node Positive Breast CancerOncologic Drug Advisory Committee INTRODUCTION

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

## 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

**Notes:**
Good morning, I am David Tuck from Clinical Oncology at Bristol-Myers Squibb PRI.  It is our pleasure to present to you today the summary of the data contained within our New Drug Application for the use of TAXOL® in the adjuvant treatment of node positive breast cancer. 
This morning the initial presentation will be made by Dr. Larry Norton who will briefly review the role of chemotherapy  in the adjuvant treatment of breast cancer.  He will be followed by Dr. Craig Henderson who will present the results of the pivotal study, Intergroup Study 0148. 
Following this, Dr. Renzo Canetta will present a brief summary and we will be pleased to answer any questions.

## 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

**Notes:**
We welcome today our external consultants, who are all associated with the Cancer and Leukemia Group B (CALGB). 
Dr. Don Berry, CALGB Breast Committee statistician and the primary statistician for the pivotal study.
Dr. Steve George, the director of the CALGB Statistical Center;
Dr. Craig Henderson, the Study Chair for the pivotal study; 
and, Dr. Larry Norton, the Chair of the CALGB Breast Committee.

## ACTIVITY IN BREAST CANCER

- TAXOL showed high response rates in Phase II trials in heavily pretreated patients, including anthracycline refractory patients
- One randomized trial (n=471) 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 (n=469) 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

**Notes:**
The pivotal trial is one of many defining the role of TAXOL in the treatment of breast cancer.

TAXOL initially was shown to have high response rates in metastatic breast cancer in Phase II trials, including heavily pretreated patients and including anthracycline refractory patients.

A 471 patient randomized study led to the initial approval in 1994 of TAXOL for the second line treatment of metastatic disease using a dose of 175 mg/m2 administered over 3 hours.

In 1998 Herceptin, based on a randomized trial which included 469 patients, was approved to be used in combination with TAXOL, using a dose of 175 mg/m2 administered over 3 hours, for the first line treatment of HER2+ metastatic breast cancer.

## 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

**Notes:**
The pivotal trial to be discussed today is an intergroup trial, INT-0148 which evaluated doxorubicin dose escalation as well as the sequential addition of TAXOL versus no further therapy as part of the Cyclophosphamide/Doxorubicin adjuvant chemotherapy regimen for node positive breast cancer.

The Coordinating Group for this study was the CALGB.

Participating groups included the Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group.

A total of 3,170 patients were accrued to this study from May 1, 1994 to April 15, 1997.

## 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

**Notes:**
The pivotal study is the largest randomized trial of chemotherapy in the adjuvant treatment of node positive breast cancer ever submitted to the FDA.

As you will hear today, this study demonstrates that TAXOL therapy, given with the same dose schedule of 175 mg/m2 over 3 hours, provides significant advantages in both disease-free and overall survival when added sequentially to standard therapy.

The safety profile in this study is consistent with the dosage administered.

## PROPOSED INDICATION

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

**Notes:**
These results lead to the proposed indication for the use of TAXOL administered sequential to standard combination chemotherapy for the adjuvant treatment of node positive breast cancer.

And now, Dr. Larry Norton will comment on current approaches to the adjuvant treatment of breast cancer.

## Slide 9