Arimidex/Tamoxifen Neo Adjuvant Study in Premenopausal Patients With Breast Cancer Under Anti Hormonal Treatment

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00605267
• Collaborator: (none)
• Enrollment: 197
• Locations: 4
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 49.3
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this multi-centre, randomised, double-blind, parallel-group study is to compare efficacy and safety between anastrozole and tamoxifen in pre- and post-operative administration under goserelin acetate treatment for premenopausal breast cancer patients

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Tamoxifen; Drug: Anastrazole (Arimidex); Drug: Goserelin acetate (Zoladex)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 197 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Multi-centre, Randomised, Double-blind, Parallel-group Study to Compare Efficacy and Safety Between Anastrozole (ZD1033) and Tamoxifen in Pre- and Post-operative Administration Under Goserelin Acetate Treatment for Premenopausal Breast Cancer Patients
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Tamoxifen	Drug: Tamoxifen; 20 mg once daily oral dose; Other Names: NOLVADEX ; Drug: Goserelin acetate (Zoladex); 3.6mg/month depot injection; Other Names: ZOLADEX
Experimental: 2 Anastrazole (Arimidex)	Drug: Anastrazole (Arimidex); 1 mg once daily oral dose; Other Names: ARIMIDEX ZD1033 ; Drug: Goserelin acetate (Zoladex); 3.6mg/month depot injection; Other Names: ZOLADEX

Outcome Measures

Primary Outcome Measures

1. Best Overall Response Rate (BORR) (Calliper) [24 weeks]

   The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from calliper measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by Calliper: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

2. Best Overall Response Rate (BORR) (US) [24 weeks]

   The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from ultra sound (US) measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by US: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. Best Overall Response Rate (BORR) (MRI/CT) [24 weeks]

   The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period(based on the data from magnetic resonance imaging (MRI) or computed tomography (CT) measurement). CR (or PR) criteria are met at either 12 weeks or 24 weeks. Per RECIST Criteria (V1.0) and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Bone Mineral Density (BMD) Lumbar Spine [Assessed at baseline and after 24 weeks of treatment]

   Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at lumbar spine.

2. Bone Mineral Density (BMD) Cervical Thighbone [Assessed at baseline and after 24 weeks of treatment]

   Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at cervical thighbone.

3. Bone Turnover Marker (BAP) EIA Method [Assessed at baseline and after 24 weeks of treatment]

   Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method

4. Bone Turnover Marker (BAP) CLEIA Method [Assessed at baseline and after 24 weeks of treatment]

   Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method

5. Bone Turnover Marker (NTX) [Assessed at baseline and after 24 weeks of treatment]

   Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks

6. Serum Oestrone (E1) Concentrations [Assessed at baseline and after 24 weeks of treatment]

   Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks.

7. Serum Oestradiol (E2) Concentrations [Assessed at baseline and after 24 weeks of treatment]

   Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks.

8. Oestrogen Receptor (ER) Status [Assessed at baseline and after 24 weeks of treatment]

   ER status in the ITT population is categorized as Positive or Negative

9. Progesterone Receptor (PgR) Status [Assessed at baseline and after 24 weeks of treatment]

   PgR status in the ITT population is categorized as Positive or Negative.

10. Human Epidermal Growth Factor Receptor 2 (HER2) Status [Assessed at baseline and after 24 weeks of treatment]

    HER2 status in the ITT population is categorized as Positive or Negative

11. Histopathological Response Rate (HRR) [Assessed at baseline and after 24 weeks of treatment]

    Number of patients in the ITT population defined as histopathological responders over the total number of patients x 100. An histopathological responder = a patient classified as Grade 1b, 2 or 3 for the histopathological response (Grade 0 = no response, 1a = mild response, 1b = moderate response, 2 = marked response or 3 = complete response)

12. Functional Assessment of Cancer Therapy-Breast (FACT-B) [Assessed at baseline and after 24 weeks of treatment]

    Change from baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B)in the ITT population at 24 weeks. Trial Outcome Index (TOI) = the sum of the Physical Well-Being (PWB), Functional Well-Being (FWB), and Breast Cancer Scale (BCS) subscales of FACT-B. FACT-B includes 36 questions; 7 in PWB (Physical Well-Being); 7 inSWB (Social / Family Well-Being); 6 in EWB (Emotional Well-Being); 7 in FWB (Functional Well-Being); 9 in BCS (Breast Cancer Subscale). Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI.

13. Endocrine Subscale (ES) [Assessed at baseline and after 24 weeks of treatment]

    Change from baseline in Endocrine Symptom Subscale (ES)) in the ITT population at 24 weeks. ES score = the sum of the responses to all the questions on ES, low scores reflect poor quality of life and high scores reflects better quality of life. Score range: 0-72

14. Anastrozole Plasma Concentrations (Cmin) [Assessed at week 12]

    Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Premenopausal, estrogen receptor positive women, aged 20 years and over, with operable and measurable breast cancer who have provided written informed consent

Exclusion Criteria:

• Medical history of chemotherapy or endocrine therapy for breast cancer, or with treatment history of radiotherapy. Unwillingness to stop taking any drug known to affect sex hormone status (including hormone replacement therapy (HRT).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Hakata	Fukuoka	Japan
2	Research Site	Kumamoto		Japan
3	Research Site	Nagoya		Japan
4	Research Site	Osaka		Japan

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Toshiyuki Kihara, Clinical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00605267
• Other Study ID Numbers: D539BC00001
• First Posted: Jan 31, 2008
• Last Update Posted: Sep 6, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by AstraZeneca: Breast Cancer; Breast Neoplasms; Tumors or cancer of the human BREAST; Tumor or cancer of the human MAMMARY GLAND
• Additional relevant MeSH terms: Breast Neoplasms; Tamoxifen; Goserelin; Anastrozole

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 4 research sites in Japan: Hakata (Fukuoka), Kumamoto (Kumamoto), Nagoya (Nagoya), Osaka (Osaka). The study initiation date was October 2007 and the study completion date was January 2010.
Pre-assignment Detail	A total of 197 participants were recruited into this study and 98 were randomized to Anastrozole (20 mg once daily oral dose) and 99 were randomized to Tamoxifen (1 mg once daily oral dose) with one subject voluntarily discontinuing prior to receiving treatment Tamoxifen.

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Period Title: Overall Study
STARTED	98	99
COMPLETED	95	90
NOT COMPLETED	3	9

Baseline Characteristics

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg	Total
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Total of all reporting groups
Overall Participants	98	99	197
Age, Customized (Number) [Number]
20-29 years	2 2%	0 0%	2 1%
30-39 years	21 21.4%	20 20.2%	41 20.8%
40-49 years	65 66.3%	68 68.7%	133 67.5%
50-59 years	10 10.2%	11 11.1%	21 10.7%
Sex: Female, Male (Count of Participants)
Female	98 100%	99 100%	197 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Best Overall Response Rate (BORR) (Calliper)
Description	The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from calliper measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by Calliper: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period. At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	98	99
Number [Percentage of Participants]	70.4 71.8%	50.5 51%

2. Primary Outcome

Title	Best Overall Response Rate (BORR) (US)
Description	The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period (based on the data from ultra sound (US) measurement). CR (or PR) criteria are met at 2 or more time in points every 4 weeks. Per RECIST Criteria (V1.0) and assessed by US: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	98	99
Number [Participants]	58.2 59.4%	42.4 42.8%

3. Primary Outcome

Title	Best Overall Response Rate (BORR) (MRI/CT)
Description	The BORR were defined as the percentage of patients with confirmed CR or PR in the ITT population during 24 weeks pre-operative treatment period(based on the data from magnetic resonance imaging (MRI) or computed tomography (CT) measurement). CR (or PR) criteria are met at either 12 weeks or 24 weeks. Per RECIST Criteria (V1.0) and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	98	99
Number [Percentage of Participants]	64.3 65.6%	37.4 37.8%

4. Secondary Outcome

Title	Bone Mineral Density (BMD) Lumbar Spine
Description	Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at lumbar spine.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

The standard BMD value is defined by Japanese Osteoporosis Society in the table of reference values showing the mean for the age, gender, race, skeletal site, and densitometer measurement units was used. Then the formula was used at each measurement data: BMD(%) = Patient's BMD / standard BMD) x 100

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	80	78
Mean (Standard Deviation) [PercentageBMD=Patient's BMD/standard BMD]	-5.8 (3.4)	-2.9 (2.5)

5. Secondary Outcome

Title	Bone Mineral Density (BMD) Cervical Thighbone
Description	Change from baseline in Bone Mineral Density value (percentage), in all subjects who used DXA(Dual-energy X-ray absorptiometry) method throughout the study, at 24 weeks measured at cervical thighbone.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Difference of percentage Bone Mineral Density (BMD) Cervical Thighbone = BMD percentage at 24 weeks - BMD percentage at baseline

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	80	77
Mean (Standard Deviation) [PercentageBMD=Patient'sBMD/standard BMD)]	-2.5 (5.1)	-0.5 (3.2)

6. Secondary Outcome

Title	Bone Turnover Marker (BAP) EIA Method
Description	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by EIA method
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	59	60
Mean (Standard Deviation) [U/L]	7.1941 (6.1600)	0.7333 (3.3640)

7. Secondary Outcome

Title	Bone Turnover Marker (BAP) CLEIA Method
Description	Change from baseline in serum Bone-Alkaline Phosphatase (BAP) at 24 weeks measured by CLEIA method
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	36	30
Mean (Standard Deviation) [ug/L]	3.96 (4.60)	-0.75 (3.10)

8. Secondary Outcome

Title	Bone Turnover Marker (NTX)
Description	Change from baseline in serum crosslinked N-Telopeptide of type I collagen (NTX) at 24 weeks
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	95	89
Mean (Standard Deviation) [nmolBCE(Bone Collagen Equivalent) /L]	9.17 (4.74)	2.59 (3.23)

9. Secondary Outcome

Title	Serum Oestrone (E1) Concentrations
Description	Ratio of serum Oestrone (E1) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	96	92
Mean (Standard Deviation) [Ratio]	0.028 (0.036)	0.341 (0.282)

10. Secondary Outcome

Title	Serum Oestradiol (E2) Concentrations
Description	Ratio of serum Oestradiol (E2) concentration (pg/mL) in the ITT population from baseline at 24 weeks.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	96	92
Mean (Standard Deviation) [Ratio]	0.041 (0.092)	0.082 (0.186)

11. Secondary Outcome

Title	Oestrogen Receptor (ER) Status
Description	ER status in the ITT population is categorized as Positive or Negative
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	94	90
Baseline Positive & 24 weeks Negative	2 2%	1 1%
Baseline Positive & 24 weeks Positive	92 93.9%	89 89.9%
Baseline Negative & 24 weeks Negative	0 0%	0 0%
Baseline Negative & 24 weeks Positive	0 0%	0 0%

12. Secondary Outcome

Title	Progesterone Receptor (PgR) Status
Description	PgR status in the ITT population is categorized as Positive or Negative.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	94	90
Baseline Positive & 24 weeks Negative	60 61.2%	19 19.2%
Baseline Positive & 24 weeks Positive	29 29.6%	59 59.6%
Baseline Negative & 24 weeks Negative	4 4.1%	9 9.1%
Baseline Negative & 24 weeks Positive	1 1%	3 3%

13. Secondary Outcome

Title	Human Epidermal Growth Factor Receptor 2 (HER2) Status
Description	HER2 status in the ITT population is categorized as Positive or Negative
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	94	90
Baseline Positive & 24 weeks Negative	0 0%	0 0%
Baseline Positive & 24 weeks Positive	0 0%	0 0%
Baseline Negative & 24 weeks Negative	92 93.9%	88 88.9%
Baseline Negative & 24 weeks Positive	2 2%	2 2%

14. Secondary Outcome

Title	Histopathological Response Rate (HRR)
Description	Number of patients in the ITT population defined as histopathological responders over the total number of patients x 100. An histopathological responder = a patient classified as Grade 1b, 2 or 3 for the histopathological response (Grade 0 = no response, 1a = mild response, 1b = moderate response, 2 = marked response or 3 = complete response)
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	98	99
Number [Percentage of Participants]	41.8 42.7%	27.3 27.6%

15. Secondary Outcome

Title	Functional Assessment of Cancer Therapy-Breast (FACT-B)
Description	Change from baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B)in the ITT population at 24 weeks. Trial Outcome Index (TOI) = the sum of the Physical Well-Being (PWB), Functional Well-Being (FWB), and Breast Cancer Scale (BCS) subscales of FACT-B. FACT-B includes 36 questions; 7 in PWB (Physical Well-Being); 7 inSWB (Social / Family Well-Being); 6 in EWB (Emotional Well-Being); 7 in FWB (Functional Well-Being); 9 in BCS (Breast Cancer Subscale). Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. Score range; 0-28 in PWB; 0-28 in SWB; 0-24 in EWB; 0-28 in FWB; 0-36 in BCS; 0-92 in TOI.
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Total score of subscores or TOI is calculated from each score of question. Higher score means better and lower score means worthier. PWB, FWB and BCS were assessed in this study. TOI was a total of PWB, FWB and BCS.

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	95	92
Mean (Standard Deviation) [Trial Outcome Index (TOI) (Prorated)]	-4.42 (11.07)	-2.65 (8.09)

16. Secondary Outcome

Title	Endocrine Subscale (ES)
Description	Change from baseline in Endocrine Symptom Subscale (ES)) in the ITT population at 24 weeks. ES score = the sum of the responses to all the questions on ES, low scores reflect poor quality of life and high scores reflects better quality of life. Score range: 0-72
Time Frame	Assessed at baseline and after 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Difference of Endocrine Subscale (ES) = ES at 24 weeks - ES at baseline.

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	92	91
Mean (Standard Deviation) [ES score]	-8.85 (8.69)	-6.27 (8.93)

17. Secondary Outcome

Title	Anastrozole Plasma Concentrations (Cmin)
Description	Trough Plasma concentrations (Cmin) of Anastrozole - only Anastrozole arm was evaluated for Trough Plasma concentrations.
Time Frame	Assessed at week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anastrozole 1 mg	Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection	Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
Measure Participants	28	0
Geometric Mean (Full Range) [ng/mL]	29.7

Adverse Events

Adverse Event Reporting Description	One subject voluntarily discontinued prior to receiving treatment to Tamoxifen
Arm/Group Title	Anastrozole 1 mg		Tamoxifen 20 mg
Arm/Group Description	Anastrozole (investigational product) 1mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection		Tamoxifen (comparator) 20mg tablet given once a day orally and goserelin acetate 3.6 mg/ month depot injection
All Cause Mortality
	Anastrozole 1 mg		Tamoxifen 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anastrozole 1 mg		Tamoxifen 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/98 (1%)		0/98 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Neoplasm	1/98 (1%)		0/98 (0%)
Other (Not Including Serious) Adverse Events
	Anastrozole 1 mg		Tamoxifen 20 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/98 (88.8%)		84/98 (85.7%)
Gastrointestinal disorders
Constipation	4/98 (4.1%)		13/98 (13.3%)
Abdominal Pain Upper	5/98 (5.1%)		6/98 (6.1%)
General disorders
Fatigue	4/98 (4.1%)		5/98 (5.1%)
Infections and infestations
Nasopharyngitis	27/98 (27.6%)		24/98 (24.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	35/98 (35.7%)		20/98 (20.4%)
Musculoskeletal Stiffness	21/98 (21.4%)		9/98 (9.2%)
Joint Stiffness	5/98 (5.1%)		1/98 (1%)
Myalgia	5/98 (5.1%)		1/98 (1%)
Nervous system disorders
Headache	20/98 (20.4%)		15/98 (15.3%)
Dizziness	3/98 (3.1%)		5/98 (5.1%)
Hypoaesthesia	5/98 (5.1%)		3/98 (3.1%)
Psychiatric disorders
Insomnia	7/98 (7.1%)		9/98 (9.2%)
Reproductive system and breast disorders
Menopausal Symptoms	6/98 (6.1%)		4/98 (4.1%)
Metrorrhagia	5/98 (5.1%)		2/98 (2%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	4/98 (4.1%)		8/98 (8.2%)
Rash	5/98 (5.1%)		3/98 (3.1%)
Vascular disorders
Hot Flush	51/98 (52%)		52/98 (53.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.