Stakeholder Insight: Breast Cancer - Changing Treatment Paradigms for Local and Locally Advanced Breast Cancer

TABLE OF CONTENTS

• About Datamonitor Healthcare
• About the Oncology pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

CHAPTER 2 EPIDEMIOLOGY

• US
• Japan
• France
• Germany
• Italy
• Spain
• UK

CHAPTER 3 TUMOR CHARACTERISTICS

• Introduction
• Hormone-receptor status
• Almost all patients are checked for ER status...
• ... except in Italy
• Fewer patients are tested for PgR status
• HER2 status
• IHC and FISH

CHAPTER 4 NEOADJUVANT THERAPY IN LOCAL AND LOCALLY ADVANCED BREAST CANCER

• Introduction
• Randomized clinical trials of neoadjuvant therapy
• Neoadjuvant therapy - no survival advantage but decrease in mastectomy rates
• Sequential docetaxel adds a new dimension
• The Aberdeen trial
• NSABP B-27
• The GEPAR-DUO study
• The Consensus Conference on Neoadjuvant Chemotherapy in Carcinoma of the Breast
• The use of neoadjuvant therapy in local and locally advanced breast cancer in the seven major markets
• Limited use of neoadjuvant therapy in local stage
• More common in locally advanced stage
• Minimal difference between stages in Japan
• Also low usage in Germany
• High in Spain
• Significant increase in neoadjuvant chemotherapy in recent years
• Neoadjuvant chemotherapy regimens
• Localized breast cancer
• Doxorubicin-based regimens is prominent in the US, Italy and Spain...
• Relatively low use of anthracyclines in Italy
• Taxane usage in the neoadjuvant setting
• Paclitaxel is more commonly used in the US and Japan
• Docetaxel-based regimens are more common in Europe
• Locally advanced breast cancer
• Drug regimens remain similar across the stages

CHAPTER 5 ADJUVANT THERAPY IN LOCAL AND LOCALLY ADVANCED BREAST CANCER

• Introduction
• Clinical trials for adjuvant chemotherapy
• The advent of the taxanes
• The use of adjuvant therapy in local and locally advanced breast cancer in the seven major markets
• Fewer patients treated with adjuvant therapy in Japan
• Adjuvant chemotherapy regimens
• Localized breast cancer
• Adjuvant regimens remain similar to neoadjuvant regimens
• Doxorubicin-based regimens are also commonly used in Italy and Spain
• Epirubicin-based regimens are preferred in the other markets
• High taxane usage in the US and Spain
• Minimal usage in the UK
• Locally advanced breast cancer
• Anthracycline usage remains broadly similar between stages
• Increase in taxane usage in locally advanced stage
• Docetaxel to become the gold standard in France
• Fluorouracil-based regimens
• Varying usage of fluorouracil
• Taxanes over fluorouracil in the US
• 5-FU versus capecitabine
• Limited market penetration of capecitabine
• Taxanes administration schedules
• Three-weekly regimens still predominantly used
• High usage of weekly taxane regimen in Japan
• Dose-dense regimen usage in the US and Spain is also high

CHAPTER 6 HORMONAL THERAPY

• Introduction
• Hormone-receptor status
• Fewer HR-positive patients treated with antihormonals in Japan
• Some hormone-negative patients treated with antihormonals
• Menopausal status
• Premenopausal breast cancer patients
• Ovarian ablation
• LHRH agonists are mainly used as ovarian suppression
• Half of patients do not undergo ovarian ablation
• Postmenopausal breast cancer patients
• Tamoxifen still dominates...
• ...but anastrozole will become the gold standard
• Barriers to the uptake of anastrozole
• Other aromatase inhibitors only play a minor role
• Femara (letrozole)
• Aromasin (exemestane)
• Switch from tamoxifen
• Japanese physicians more readily switch to anastrozole
• Subsequent letrozole therapy common in the US and France
• Exemestane remains underused
• The majority of patients do not switch
• "Renaissance" of the antihormonals market

CHAPTER 7 PIPELINE DRUGS

• Introduction
• Physician awareness of pipeline drugs
• Abraxane (albumin-bound paclitaxel)
• Physician awareness of Abraxane
• Physician rating of Abraxane
• RPR109881 (taxane)
• Physician awareness of RPR109881
• Physician rating of RPR109881
• Ixabepilone (epothilone B)
• Physician awareness of ixabepilone
• Physician rating of ixabepilone
• Evista (raloxifene)
• Physician awareness of Evista
• Physician rating of Evista
• Atamestane
• Physician awareness of atamestane
• Physician rating of atamestane
• Lapatinib (GW572016)
• Physician awareness of lapatinib
• Physician rating of lapatinib
• IGN-101
• Physician awareness of IGN-101
• Physician rating of IGN-101
• Other drugs
• Physician awareness of other pipeline drugs
• Physician rating of other pipeline drugs
• Comparative ratings of key pipeline drugs
• Neoadjuvant setting
• Adjuvant setting
• Metastatic setting

CHAPTER 8 APPENDIX

• Supplementary data
• Questionnaire
• Respondent breakdown
• Opinion leader interview transcript
• Definition of breast cancer
• Types of breast cancer
• Ductal carcinoma in situ (DCIS)
• Lobular carcinoma in situ (LCIS)
• Pagets disease
• Male breast cancer
• Progression of breast cancer
• Genetics of breast cancer
• Diagnosis
• Major prognostic factors
• Hormone receptor status
• Lymph node involvement
• Histologic grade
• HER-2/neu status
• S-phase status
• Standard treatment options
• Stage I
• Stage II
• Stage III
• Stage IV
• Overview of current drug therapy options
• Chemotherapy
• Hormonal therapy
• Treatment of advanced disease
• References
• About Datamonitor
• About Datamonitor Healthcare
• About the Oncology analysis team
• Disclaimer
• List of Tables
• Table 1: TNM staging in breast cancer: stage groupings
• Table 2: Percentage of local and locally advanced breast cancer patients undergoing tests for hormone receptor status in the seven major markets
• Table 3: Percentage of reasons for not testing ER status in local and locally advanced breast cancer patients in Italy
• Table 4: Percentage of local and locally advanced breast cancer patients undergoing tests for HER2 status
• Table 5: Percentage of reasons for not using HER2 test in local and locally advanced breast cancer patients in the seven major markets
• Table 6: Percentage of local and locally advanced breast cancer patients undergoing IHC and FISH tests in the seven major markets
• Table 7: Summary of randomized clinical trials for neoadjuvant therapy in breast cancer which failed to show survival advantage
• Table 8: Summary results of sequential docetaxel as neoadjuvant therapy in locally advanced breast cancer
• Table 9: Percentage of local and locally advanced breast cancer patients undergoing neoadjuvant therapy in the seven major markets
• Table 10: Percentage use of top three neoadjuvant chemotherapy regimens in local stage in the seven major markets
• Table 11: Percentage use of doxorubicin- and epirubicin-based neoadjuvant regimens in local breast cancer in the seven major markets
• Table 12: Percentage use of paclitaxel- and docetaxel-based neoadjuvant regimens in local breast cancer in the seven major markets
• Table 13: Percentage use of top three neoadjuvant drug regimens in locally advanced stage in the seven major markets
• Table 14: Percentage use of doxorubicin- and epirubicin-based neoadjuvant regimens in locally advanced breast cancer in the seven major markets
• Table 15: Percentage use of paclitaxel- and docetaxel-based neoadjuvant regimens in locally advanced breast cancer in the seven major markets
• Table 16: Percentage of local and locally advanced breast cancer patients undergoing adjuvant therapy in the seven major markets
• Table 17: Percentage use of top three adjuvant chemotherapy regimens in local stage in the seven major markets
• Table 18: Percentage use of doxorubicin- and epirubicin-based adjuvant regimens in localized breast cancer in the seven major markets
• Table 19: Percentage use of paclitaxel- and docetaxel-based adjuvant regimens in localized breast cancer in the seven major markets
• Table 20: Percentage use of top three adjuvant drug regimens in locally advanced stage in the seven major markets
• Table 21: Percentage use of doxorubicin- and epirubicin-based adjuvant regimens in locally advanced breast cancer in the seven major markets
• Table 22: Percentage use of paclitaxel- and docetaxel-based adjuvant regimens in locally advanced breast cancer in the seven major markets
• Table 23: Percentage use of fluorouracil-based adjuvant regimens in localized and locally advanced breast cancer
• Table 24: Percentage of localized and locally advanced patients treated with fluorouracil-based adjuvant regimens receiving 5-FU and Xeloda
• Table 25: Percentage of adjuvant patients treated with weekly, bi-weekly or three-weekly taxane regimens in the seven major markets
• Table 26: Percentage of local and locally advanced breast cancer patients receiving antihormonal therapy depending on HR status
• Table 27: Percentage of local and locally advanced premenopausal patients undergoing ovarian ablation
• Table 28: Percentage of local and locally advanced postmenopausal patients treated with antihormonal drugs in the seven major markets
• Table 29: Percentage of patients undergoing tamoxifen treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Table 30: Percentage of patients undergoing anastrozole treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Table 31: Percentage of patients undergoing letrozole treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Table 32: Percentage of patients undergoing exemestane treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Table 33: Percentage of patients switching from tamoxifen to aromatase inhibitors in the seven major markets
• Table 34: Late-phase pipeline drug summary
• Table 35: Percentage of physicians aware of Abraxane
• Table 36: Physician rating of Abraxane
• Table 37: Percentage of physicians aware of RPR109881
• Table 38: Physician rating of RPR109881
• Table 39: Percentage of physicians aware of ixabepilone
• Table 40: Physician rating of ixabepilone
• Table 41: Percentage of physicians aware of Evista
• Table 42: Physician rating of Evista
• Table 43: Percentage of physicians aware of atamestane
• Table 44: Physician rating of atamestane
• Table 45: Percentage of physicians aware of lapatinib
• Table 46: Physician rating of lapatinib
• Table 47: Physician awareness of IGN-101
• Table 48: Physician rating of IGN-101
• Table 49: Percentage of responses for other pipeline drugs
• Table 50: Physician rating of other pipeline drugs
• Table 51: Comparative ratings of key pipeline drugs in the neoadjuvant setting
• Table 52: Comparative ratings of key pipeline drugs in the adjuvant setting
• Table 53: Comparative ratings of key pipeline drugs in the metastatic setting
• Table 54: Percentage of localized patients receiving drug regimens in the neoadjuvant setting
• Table 55: Percentage of locally advanced patients receiving drug regimens in the neoadjuvant setting
• Table 56: Percentage of localized patients receiving drug regimens in the adjuvant setting
• Table 57: Percentage of locally advanced patients receiving drug regimens in the adjuvant setting
• Table 58: Respondent breakdown
• Table 59: Adjuvant therapy guidelines for breast cancer
• Table 60: Dosing schedules for adjuvant and first-line breast cancer chemotherapy regimens
• Table 61: Dosing schedules for breast cancer antihormonal therapies
• Table 62: Second-line treatment dosing schedules for breast cancer
• Table 63: Dosing schedules for Herceptin regimens
• List of Figures
• Figure 1: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in the US
• Figure 2: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in Japan
• Figure 3: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in France
• Figure 4: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in Germany
• Figure 5: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in Italy
• Figure 6: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in Spain
• Figure 7: Number of local and locally advanced breast cancer patients diagnosed, tested and treated in the UK
• Figure 8: Clinical outcomes according to hormone-receptor status
• Figure 9: Percentage of local and locally advanced breast cancer patients undergoing tests for hormone receptor status in the seven major markets
• Figure 10: Percentage of reasons for not testing ER status in local and locally advanced breast cancer patients in Italy
• Figure 11: Percentage of reasons for not testing PgR status in local and locally advanced breast cancer patients in the UK
• Figure 12: Percentage of local and locally advanced breast cancer patients undergoing tests for HER2 status
• Figure 13: Percentage of reasons for not using HER2 test in local and locally advanced breast cancer patients
• Figure 14: Percentage of local and locally advanced breast cancer patients undergoing IHC and FISH tests in the seven major markets
• Figure 15: Percentage of local and locally advanced breast cancer patients undergoing neoadjuvant therapy in the seven major markets
• Figure 16: Percentage use of top three neoadjuvant chemotherapy regimens in local stage in the seven major markets
• Figure 17: Percentage use of doxorubicin- and epirubicin-based neoadjuvant regimens in local breast cancer in the seven major markets
• Figure 18: Percentage use of paclitaxel- and docetaxel-based neoadjuvant regimens in local breast cancer in the seven major markets
• Figure 19: Percentage use of top three neoadjuvant drug regimens in locally advanced stage in the seven major markets
• Figure 20: Percentage use of doxorubicin- and epirubicin-based neoadjuvant regimens in locally advanced breast cancer in the seven major markets
• Figure 21: Percentage use of paclitaxel- and docetaxel-based neoadjuvant regimens in locally advanced breast cancer in the seven major markets
• Figure 22: Percentage of local and locally advanced breast cancer patients undergoing adjuvant therapy in the seven major markets
• Figure 23: Percentage use of top three adjuvant chemotherapy regimens in local stage in the seven major markets
• Figure 24: Percentage use of doxorubicin- and epirubicin-based adjuvant regimens in localized breast cancer in the seven major markets
• Figure 25: Percentage use of paclitaxel- and docetaxel-based adjuvant regimens in localized breast cancer in the seven major markets
• Figure 26: Percentage use of top three adjuvant drug regimens in locally advanced stage in the seven major markets
• Figure 27: Percentage use of doxorubicin- and epirubicin-based adjuvant regimens in locally advanced breast cancer in the seven major markets
• Figure 28: Percentage use of paclitaxel- and docetaxel-based adjuvant regimens in locally advanced breast cancer in the seven major markets
• Figure 29: Percentage use of fluorouracil-based adjuvant regimens in localized and locally advanced breast cancer
• Figure 30: Percentage of localized and locally advanced patients treated with fluorouracil-based adjuvant regimens receiving 5-FU and Xeloda
• Figure 31: Percentage of adjuvant patients treated with weekly, two-weekly or three-weekly taxane regimens in the seven major markets
• Figure 32: Percentage of local and locally advanced breast cancer patients receiving antihormonal therapy depending on HR status
• Figure 33: Summary of treatment strategy for pre- and postmenopausal breast cancer patients
• Figure 34: Percentage of local and locally advanced premenopausal patients undergoing ovarian ablation
• Figure 35: Percentage of local and locally advanced postmenopausal patients treated with antihormonal drugs in the seven major markets
• Figure 36: Percentage of patients undergoing tamoxifen treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Figure 37: Percentage of patients undergoing anastrozole treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Figure 38: Percentage of patients undergoing letrozole treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Figure 39: Percentage of patients undergoing exemestane treatment for less than two years, between two and five years, and more than five years, in the seven major markets
• Figure 40: Percentage of patients switching from tamoxifen to aromatase inhibitors in the seven major markets
• Figure 41: Percentage of physicians aware of Abraxane
• Figure 42: Physician rating of Abraxane
• Figure 43: Percentage of physicians aware of RPR109881
• Figure 44: Physician rating of RPR109881
• Figure 45: Percentage of physicians aware of ixabepilone
• Figure 46: Physician rating of ixabepilone
• Figure 47: Percentage of physicians aware of Evista
• Figure 48: Physician rating of Evista
• Figure 49: Percentage of physicians aware of atamestane
• Figure 50: Physician rating of atamestane
• Figure 51: Percentage of physicians aware of lapatinib
• Figure 52: Physician rating of lapatinib
• Figure 53: Physician awareness of IGN-101
• Figure 54: Physician rating of IGN-101
• Figure 55: Percentage of responses for other pipeline drugs
• Figure 56: Physician rating of other pipeline drugs
• Figure 57: Comparative ratings of key pipeline drugs in the neoadjuvant setting
• Figure 58: Comparative ratings of key pipeline drugs in the adjuvant setting
• Figure 59: Comparative ratings of key pipeline drugs in the metastatic setting