FIRST: A Clinical Trial to Compare Efficacy and Tolerability of Faslodex With Arimidex in Patients With Advanced Breast Cancer

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00274469
• Collaborator: (none)
• Enrollment: 205
• Locations: 41
• Arms: 2
• Actual Duration (Months): 131.2
• Patients Per Site: 5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and tolerability of Faslodex (fulvestrant) with Arimidex (anastrozole) in postmenopausal women with hormone receptor positive advanced breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: fulvestrant; Drug: anastrozole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Parallel-Group, Multicentre, Phase II Study to Compare the Efficacy and Tolerability of Fulvestrant (FASLODEX™) 500 mg With Anastrozole (ARIMIDEX™) 1 mg as First Line Hormonal Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer
• Actual Study Start Date: Feb 6, 2006
• Actual Primary Completion Date: Jan 10, 2008
• Actual Study Completion Date: Jan 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Fulvestrant	Drug: fulvestrant; 500 mg intramuscular injection; Other Names: Faslodex ZD9238
Active Comparator: 2 Anastrozole	Drug: anastrozole; 1 mg oral tablet; Other Names: Arimidex ZD1033

Outcome Measures

Primary Outcome Measures

1. Clinical Benefit Rate [From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.]

   A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB.

Secondary Outcome Measures

1. Objective Response Rate [From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.]

   For each patient with measurable disease at baseline, the determination of the overall response for each visit was carried out using a SAS program per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesion (TL) and non-target lesions (NTLs) and no new lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameter of TLs (compared to baseline), no progression of NTLs and no new lesions. Objective response rate is defined as percentage of patients with either CR or PR.

2. Time to Progression [From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.]

   Time from randomization until earlier of disease progression or death. Progression was defined according to RECIST: a patient is determined to have progressed if they have progression of target lesions, clear progression of existing non-target lesions, or the appearance of one or more new lesions. Progression of target lesions is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum of LD recorded. Kaplan-Meier estimates of median for each treatment are reported.

3. Time to Treatment Failure [From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.]

   Time from randomization to treatment discontinuation

4. Time to Progression (Investigator Assessed) [From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.]

   Time from randomization to disease progression (investigator assessed) or death from any cause. Progression was defined by investigator opinion, as patients did not have formal RECIST visits in the follow-up period after the data cut off for the primary analysis of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 100 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed hormone receptor positive advanced breast cancer, postmenopausal women

Exclusion Criteria:

• Previous treatment for advanced breast cancer (previous treatment for early breast cancer is allowed).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Frederick	Maryland	United States	21701
2	Research Site	Saint Louis	Missouri	United States	63113
3	Research Site	Teaneck	New Jersey	United States	07666
4	Research Site	Austin	Texas	United States	78705
5	Research Site	Duncanville	Texas	United States	75137
6	Research Site	Barretos		Brazil	14784-400
7	Research Site	Belo Horizonte		Brazil	30380-490
8	Research Site	Goiânia		Brazil	74000-000
9	Research Site	Jaú		Brazil	17210-120
10	Research Site	Rio de Janeiro		Brazil	20560-120
11	Research Site	Sao Paulo		Brazil	01219-010
12	Research Site	Blagoevgrad		Bulgaria	2700
13	Research Site	Plovdiv		Bulgaria	4000
14	Research Site	Shumen		Bulgaria	9700
15	Research Site	Sofia		Bulgaria	1233
16	Research Site	Sofia		Bulgaria	1527
17	Research Site	Sofia		Bulgaria	1784
18	Research Site	Varna		Bulgaria	9000
19	Research Site	Veliko Tarnovo		Bulgaria	5000
20	Research Site	Vratza		Bulgaria	3000
21	Research Site	Brno		Czechia	656 53
22	Research Site	Brno		Czechia	656 91
23	Research Site	Jicin		Czechia	506 43
24	Research Site	Ostrava		Czechia	708 52
25	Research Site	Praha 4		Czechia	140 00
26	Research Site	Usti nad Labem		Czechia	401 13
27	Research Site	Nice		France	06100
28	Research Site	Poitiers		France	86000
29	Research Site	Saint-cloud		France	92210
30	Research Site	Napoli		Italy	80131
31	Research Site	Sassari		Italy	07100
32	Research Site	Kraków		Poland	31-115
33	Research Site	Olsztyn		Poland	10-228
34	Research Site	Barcelona		Spain	08003
35	Research Site	Barcelona		Spain	08025
36	Research Site	Córdoba		Spain	14004
37	Research Site	Lérida		Spain	25198
38	Research Site	Pontevedra		Spain	36002
39	Research Site	Derby		United Kingdom	DE22 3DT
40	Research Site	Dundee		United Kingdom	DD1 9SY
41	Research Site	Edinburgh		United Kingdom	EH4 2XU

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: AstraZeneca Faslodex Medical Science Director, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D6995C00006.pdf
• D6995C00006FIRSToverall_survivalRevisedCSP_4_10_December_2014_Redacted

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00274469
• Other Study ID Numbers: D6995C00006; FIRST
• First Posted: Jan 11, 2006
• Last Update Posted: Sep 6, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by AstraZeneca: oncology; cancer; breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant; Anastrozole

Study Results

Participant Flow

Recruitment Details	Postmenopausal women presenting with advanced breast cancer who had either never received endocrine therapy for advanced disease or had not received endocrine therapy in the previous 12 months in the adjuvant setting were recruited between 6th Feb 2006 and 11th July 2007.
Pre-assignment Detail	28 of the 233 enrolled patients were not randomized to treatment groups for the following reasons - 20 patients were incorrectly enrolled (ie did not comply with inclusion / exclusion criteria), 1 died, 1 had an adverse event, 4 voluntarily discontinued, 2 patients were not randomized for other non-specified reasons.

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Period Title: Overall Study
STARTED	102	103
COMPLETED	23	10
NOT COMPLETED	79	93

Baseline Characteristics

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg	Total
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg	Total of all reporting groups
Overall Participants	102	103	205
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.6 (9.0)	67.6 (9.3)	67.1 (9.1)
Sex: Female, Male (Count of Participants)
Female	102 100%	103 100%	205 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit Rate
Description	A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB.
Time Frame	From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	102	103
Number [Percentage of Participants]	72.5 71.1%	67.0 65%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Study is powered basing on 20% deficiency in benefit rate for Fulvestrant compared to Anastrozole.
Statistical Test of Hypothesis	p-Value	0.386
	Comments	Null hypothesis: Fulvestrant has no difference with Anastrozole
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.302
	Confidence Interval	(2-Sided) 95%; 0.717 to 2.380
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR>1 favours Fulvestrant

2. Secondary Outcome

Title	Objective Response Rate
Description	For each patient with measurable disease at baseline, the determination of the overall response for each visit was carried out using a SAS program per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete Response (CR): Disappearance of all target lesion (TL) and non-target lesions (NTLs) and no new lesions. Partial Response (PR): At least a 30% decrease in the sum of longest diameter of TLs (compared to baseline), no progression of NTLs and no new lesions. Objective response rate is defined as percentage of patients with either CR or PR.
Time Frame	From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Evaluable For Response Set

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	89	93
Number [Percentage of Participants]	36.0 35.3%	35.5 34.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.947
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.021
	Confidence Interval	(2-Sided) 95%; 0.556 to 1.874
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR>1 favours Fulvestrant

3. Secondary Outcome

Title	Time to Progression
Description	Time from randomization until earlier of disease progression or death. Progression was defined according to RECIST: a patient is determined to have progressed if they have progression of target lesions, clear progression of existing non-target lesions, or the appearance of one or more new lesions. Progression of target lesions is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum of LD recorded. Kaplan-Meier estimates of median for each treatment are reported.
Time Frame	From randomisation to data cut off (DCO) for primary analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for primary analysis was on 10th Jan 2008, 6 months after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	102	103
Median (Inter-Quartile Range) [Day]	NA	381

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0496
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6266
	Confidence Interval	(2-Sided) 95%; 0.3929 to 0.9991
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

4. Secondary Outcome

Title	Time to Treatment Failure
Description	Time from randomization to treatment discontinuation
Time Frame	From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	102	103
Median (Inter-Quartile Range) [Day]	536	387

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Regression, Cox
	Comments	Cox regression analysis of TTTF controlling for baseline covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.52 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

5. Secondary Outcome

Title	Time to Progression (Investigator Assessed)
Description	Time from randomization to disease progression (investigator assessed) or death from any cause. Progression was defined by investigator opinion, as patients did not have formal RECIST visits in the follow-up period after the data cut off for the primary analysis of the study.
Time Frame	From randomisation to data cut off (DCO) for 75% treatment failure. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007. The DCO for 75% treatment failure was on 26 Mar 2010, 32 months after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	102	103
Median (Inter-Quartile Range) [Day]	712	400

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.47 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Regression, Cox
	Comments	Cox regression analysis of TTP (investigator assessed) controlling for baseline covariates.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

6. Post-Hoc Outcome

Title	Overall Survival
Description	Time from randomization to death (any cause)
Time Frame	From randomization to data cut off (DCO) for 65% OS analysis. The first and the last patients were enrolled on 6 Feb 2006 and 11 Jul 2007 respectively. The DCO for 65% OS analysis was on 15 Jul 2014, 7 years after the last patient was enrolled.

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Fulvestrant 500 mg	Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg	Anastrozole 1 mg
Measure Participants	102	103
Median (Inter-Quartile Range) [Month]	54.1	48.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.041
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.50 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fulvestrant 500 mg, Anastrozole 1 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.126
	Comments
	Method	Regression, Cox
	Comments	Cox regression analysis of OS controlling for baseline covariates
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	HR<1 favours Fulvestrant

Adverse Events

Time Frame	Non-serious adverse events = randomisation upto the point of data cut off for the primary efficacy analysis. Serious adverse events = randomisation up to the point of data cut off for the 65% overall survival analysis.
Adverse Event Reporting Description	First patient was enrolled on 6th Feb 2006. Non-serious AEs are reported from randomisation up to the data cut-off (DCO 10th Jan 2008) for the primary analysis (56 days after last injection and 30 days after last tablet). Serious AEs are reported from randomisation up to DCO for the 65% OS (15th July 2014). Note: All-Mortality is based on full population, while AEs and SAEs are based on safety population (1 less patient in Fulvestrant arm as it never received the randomised drug).
Arm/Group Title	Fulvestrant 500 mg		Anastrozole 1 mg
Arm/Group Description	Fulvestrant 500 mg		Anastrozole 1 mg
All Cause Mortality
	Fulvestrant 500 mg		Anastrozole 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/102 (61.8%)		74/103 (71.8%)
Serious Adverse Events
	Fulvestrant 500 mg		Anastrozole 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/101 (23.8%)		22/103 (21.4%)
Blood and lymphatic system disorders
LYMPHADENOPATHY	0/101 (0%)	0	1/103 (1%)	1
FEBRILE NEUTROPENIA	0/101 (0%)	0	1/103 (1%)	1
Cardiac disorders
ATRIAL FIBRILLATION	1/101 (1%)	1	1/103 (1%)	1
ARRHYTHMIA	0/101 (0%)	0	1/103 (1%)	1
CARDIAC FAILURE	2/101 (2%)	2	0/103 (0%)	0
CARDIAC FAILURE CONGESTIVE	0/101 (0%)	0	1/103 (1%)	2
CORONARY OSTIAL STENOSIS	0/101 (0%)	0	1/103 (1%)	1
Eye disorders
LACRIMAL DISORDER	0/101 (0%)	0	1/103 (1%)	1
BLINDNESS	1/101 (1%)	1	0/103 (0%)	0
Gastrointestinal disorders
GASTRIC ULCER	1/101 (1%)	1	0/103 (0%)	0
NAUSEA	1/101 (1%)	1	0/103 (0%)	0
VOMITING	1/101 (1%)	1	0/103 (0%)	0
ANAL HAEMRROHAGE	1/101 (1%)	1	0/103 (0%)	0
SUBILEUS	0/101 (0%)	0	1/103 (1%)	1
General disorders
ASTHENIA	1/101 (1%)	1	0/103 (0%)	0
DEATH	0/101 (0%)	0	2/103 (1.9%)	2
GENERAL PHYSICAL HEALTH DETERIORATION	0/101 (0%)	0	1/103 (1%)	1
Infections and infestations
BRONCHITIS	1/101 (1%)	2	0/103 (0%)	0
GASTROENTERITIS VIRAL	1/101 (1%)	1	0/103 (0%)	0
PNEUMONIA	0/101 (0%)	0	1/103 (1%)	1
ARTHRITIS BACTERIAL	1/101 (1%)	3	0/103 (0%)	0
EMPYEMA	0/101 (0%)	0	1/103 (1%)	1
URINARY TRACT INFECTION	1/101 (1%)	1	0/103 (0%)	0
LOWER RESPIRATORY TRACT INFECTION	1/101 (1%)	1	0/103 (0%)	0
Injury, poisoning and procedural complications
FALL	1/101 (1%)	1	0/103 (0%)	0
FEMUR FRACTURE	1/101 (1%)	1	2/103 (1.9%)	2
HUMERUS FRACTURE	0/101 (0%)	0	1/103 (1%)	1
RADIUS FRACTURE	0/101 (0%)	0	1/103 (1%)	1
FEMORAL NECK FRACTURE	1/101 (1%)	1	0/103 (0%)	0
HIP FRACTURE	0/101 (0%)	0	1/103 (1%)	1
RIB FRACTURE	0/101 (0%)	0	1/103 (1%)	1
ROAD TRAFFIC ACCIDENT	0/101 (0%)	0	1/103 (1%)	1
Metabolism and nutrition disorders
CACHEXIA	1/101 (1%)	1	0/103 (0%)	0
DECREASED APPETITE	2/101 (2%)	2	0/103 (0%)	0
DEHYDRATION	2/101 (2%)	3	0/103 (0%)	0
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	1/101 (1%)	1	0/103 (0%)	0
BONE PAIN	0/101 (0%)	0	1/103 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER	0/101 (0%)	0	1/103 (1%)	1
LUNG CANCERMETASTATIC	0/101 (0%)	0	1/103 (1%)	1
METASTASES TO THORAX	1/101 (1%)	1	0/103 (0%)	0
SARCOMA	0/101 (0%)	0	1/103 (1%)	1
SQUAMOUS CELL CARCINOMA	0/101 (0%)	0	1/103 (1%)	1
TUMOUR HAEMORRAGE	1/101 (1%)	1	0/103 (0%)	0
Nervous system disorders
NEURALGIA	1/101 (1%)	1	1/103 (1%)	1
TRANSIENT ISCHAEMIC ATTACK	0/101 (0%)	0	2/103 (1.9%)	2
CEREBROVASCULAR ACCIDENT	0/101 (0%)	0	1/103 (1%)	1
SPINAL CORD COMPRESSION	1/101 (1%)	1	0/103 (0%)	0
Psychiatric disorders
CONFUSIONAL STATE	1/101 (1%)	1	0/103 (0%)	0
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/101 (1%)	2	0/103 (0%)	0
DYSPNOEA	2/101 (2%)	2	0/103 (0%)	0
PLEURITIC PAIN	1/101 (1%)	1	0/103 (0%)	0
PULMONARY EMBOLISM	1/101 (1%)	1	0/103 (0%)	0
Skin and subcutaneous tissue disorders
ANGIOEDEMA	1/101 (1%)	1	0/103 (0%)	0
Surgical and medical procedures
CHOLECYSTECTOMY	1/101 (1%)	1	0/103 (0%)	0
Vascular disorders
HYPERTENSION	1/101 (1%)	1	0/103 (0%)	0
Other (Not Including Serious) Adverse Events
	Fulvestrant 500 mg		Anastrozole 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/101 (70.3%)		70/103 (68%)
Blood and lymphatic system disorders
ANAEMIA	2/101 (2%)	2	1/103 (1%)	1
LYMPHADENOPATHY	2/101 (2%)	2	0/103 (0%)	0
Cardiac disorders
ATRIAL FIBRILLATION	0/101 (0%)	0	1/103 (1%)	1
LEFT VENTRICULAR DYSFUNCTION	1/101 (1%)	1	0/103 (0%)	0
PALPITATIONS	0/101 (0%)	0	1/103 (1%)	1
Ear and labyrinth disorders
VERTIGO	1/101 (1%)	1	3/103 (2.9%)	4
TINNITUS	0/101 (0%)	0	2/103 (1.9%)	2
EAR PAIN	1/101 (1%)	1	0/103 (0%)	0
Endocrine disorders
GOITRE	1/101 (1%)	1	0/103 (0%)	0
Eye disorders
ACCOMMODATION DISORDER	0/101 (0%)	0	1/103 (1%)	1
CONJUNCTIVAL DISORDER	0/101 (0%)	0	1/103 (1%)	1
DIPLOPIA	1/101 (1%)	1	0/103 (0%)	0
ERYTHEMA OF EYELID	1/101 (1%)	1	0/103 (0%)	0
EXOPHTHALMOS	1/101 (1%)	1	0/103 (0%)	0
EYE PAIN	0/101 (0%)	0	1/103 (1%)	1
EYELID PTOSIS	1/101 (1%)	1	0/103 (0%)	0
MYOPIA	0/101 (0%)	0	1/103 (1%)	1
VISUAL ACUITY REDUCED	1/101 (1%)	1	0/103 (0%)	0
Gastrointestinal disorders
CONSTIPATION	10/101 (9.9%)	12	5/103 (4.9%)	5
DIARRHOEA	6/101 (5.9%)	7	7/103 (6.8%)	7
NAUSEA	10/101 (9.9%)	10	7/103 (6.8%)	8
VOMITING	8/101 (7.9%)	10	3/103 (2.9%)	4
DYSPEPSIA	2/101 (2%)	3	5/103 (4.9%)	5
ABDOMINAL PAIN	2/101 (2%)	4	2/103 (1.9%)	2
ABDOMINAL PAIN UPPER	2/101 (2%)	2	2/103 (1.9%)	2
HIATUS HERNIA	2/101 (2%)	2	2/103 (1.9%)	2
DRY MOUTH	2/101 (2%)	2	1/103 (1%)	1
ANAL DISCOMFORT	0/101 (0%)	0	2/103 (1.9%)	2
DIVERTICULUM INTESTINAL	0/101 (0%)	0	2/103 (1.9%)	2
GASTROOESOPHAGEAL REFLUX DISEASE	0/101 (0%)	0	2/103 (1.9%)	2
STOMATITIS	2/101 (2%)	2	0/103 (0%)	0
ABDOMINAL DISTENSION	0/101 (0%)	0	1/103 (1%)	1
ABDOMINAL PAIN LOWER	0/101 (0%)	0	1/103 (1%)	1
FLATULENCE	1/101 (1%)	1	0/103 (0%)	0
GASTRODUODENITIS	1/101 (1%)	1	0/103 (0%)	0
GASTROINTESTINAL PAIN	0/101 (0%)	0	1/103 (1%)	1
HAEMATEMESIS	0/101 (0%)	0	1/103 (1%)	1
HAEMORRHOIDAL HAEMORRHAGE	0/101 (0%)	0	1/103 (1%)	1
HAEMORRHOIDS	0/101 (0%)	0	1/103 (1%)	1
PROCTITIS	0/101 (0%)	0	1/103 (1%)	1
RETCHING	1/101 (1%)	1	0/103 (0%)	0
General disorders
FATIGUE	1/101 (1%)	1	8/103 (7.8%)	8
INJECTION SITE PAIN	6/101 (5.9%)	14	0/103 (0%)	0
ASTHENIA	8/101 (7.9%)	14	8/103 (7.8%)	9
OEDEMA PERIPHERAL	0/101 (0%)	0	4/103 (3.9%)	4
PYREXIA	2/101 (2%)	2	2/103 (1.9%)	2
INFLUENZA LIKE ILLNESS	3/101 (3%)	3	0/103 (0%)	0
INJECTION SITE HAEMATOMA	1/101 (1%)	3	0/103 (0%)	0
INJECTION SITE HAEMORRHAGE	1/101 (1%)	3	0/103 (0%)	0
INJECTION SITE PRURITUS	2/101 (2%)	3	0/103 (0%)	0
APPLICATION SITE PAIN	1/101 (1%)	2	0/103 (0%)	0
GENERAL PHYSICAL HEALTH DETERIORATION	1/101 (1%)	2	0/103 (0%)	0
CHILLS	1/101 (1%)	1	0/103 (0%)	0
GAIT DISTURBANCE	1/101 (1%)	1	0/103 (0%)	0
INJECTION SITE NODULE	1/101 (1%)	1	0/103 (0%)	0
IRRITABILITY	0/101 (0%)	0	1/103 (1%)	1
NON-CARDIAC CHEST PAIN	1/101 (1%)	1	0/103 (0%)	0
Hepatobiliary disorders
HEPATIC PAIN	0/101 (0%)	0	2/103 (1.9%)	2
CHOLELITHIASIS	1/101 (1%)	1	0/103 (0%)	0
HEPATIC FUNCTION ABNORMAL	0/101 (0%)	0	1/103 (1%)	1
LIVER TENDERNESS	0/101 (0%)	0	1/103 (1%)	1
Immune system disorders
CONTRAST MEDIA ALLERGY	1/101 (1%)	1	1/103 (1%)	1
SEASONAL ALLERGY	0/101 (0%)	0	2/103 (1.9%)	2
HYPERSENSITIVITY	0/101 (0%)	0	1/103 (1%)	1
Infections and infestations
INFLUENZA	1/101 (1%)	1	6/103 (5.8%)	6
URINARY TRACT INFECTION	4/101 (4%)	5	1/103 (1%)	3
BRONCHITIS	3/101 (3%)	3	3/103 (2.9%)	3
UPPER RESPIRATORY TRACT INFECTION	3/101 (3%)	3	3/103 (2.9%)	3
LOWER RESPIRATORY TRACT INFECTION	1/101 (1%)	2	3/103 (2.9%)	3
CYSTITIS	3/101 (3%)	3	1/103 (1%)	1
HERPES ZOSTER	2/101 (2%)	2	0/103 (0%)	0
ORAL CANDIDIASIS	1/101 (1%)	1	1/103 (1%)	1
SINUSITIS	0/101 (0%)	0	2/103 (1.9%)	2
TONSILLITIS	1/101 (1%)	1	1/103 (1%)	1
VIRAL UPPER RESPIRATORY TRACT INFECTION	2/101 (2%)	2	0/103 (0%)	0
WOUND INFECTION STAPHYLOCOCCAL	1/101 (1%)	1	1/103 (1%)	1
ACARIASIS	1/101 (1%)	1	0/103 (0%)	0
BACTERIAL INFECTION	0/101 (0%)	0	1/103 (1%)	1
CANDIDIASIS	1/101 (1%)	1	0/103 (0%)	0
FUNGAL INFECTION	0/101 (0%)	0	1/103 (1%)	1
IMPETIGO	0/101 (0%)	0	1/103 (1%)	1
NASOPHARYNGITIS	0/101 (0%)	0	1/103 (1%)	1
OSTEOMYELITIS	1/101 (1%)	1	0/103 (0%)	0
PNEUMONIA	0/101 (0%)	0	1/103 (1%)	1
RESPIRATORY TRACT INFECTION	1/101 (1%)	1	0/103 (0%)	0
RHINITIS	1/101 (1%)	1	0/103 (0%)	0
VIRAL INFECTION	1/101 (1%)	1	0/103 (0%)	0
WOUND INFECTION	1/101 (1%)	1	0/103 (0%)	0
Injury, poisoning and procedural complications
CONTUSION	1/101 (1%)	1	1/103 (1%)	1
THERMAL BURN	2/101 (2%)	2	0/103 (0%)	0
ANAEMIA POSTOPERATIVE	0/101 (0%)	0	1/103 (1%)	1
CONTRAST MEDIA REACTION	0/101 (0%)	0	1/103 (1%)	1
FALL	1/101 (1%)	1	0/103 (0%)	0
FEMUR FRACTURE	1/101 (1%)	1	0/103 (0%)	0
JOINT INJURY	0/101 (0%)	0	1/103 (1%)	1
LACERATION	0/101 (0%)	0	1/103 (1%)	1
POST PROCEDURAL COMPLICATION	1/101 (1%)	1	0/103 (0%)	0
PUBIC RAMI FRACTURE	1/101 (1%)	1	0/103 (0%)	0
RADIATION SKIN INJURY	0/101 (0%)	0	1/103 (1%)	1
RIB FRACTURE	1/101 (1%)	1	0/103 (0%)	0
SKELETAL INJURY	1/101 (1%)	1	0/103 (0%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/101 (1%)	3	0/103 (0%)	0
BLOOD PRESSURE INCREASED	1/101 (1%)	1	2/103 (1.9%)	2
BLOOD ALKALINE PHOSPHATASE INCREASED	1/101 (1%)	1	0/103 (0%)	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED	1/101 (1%)	1	0/103 (0%)	0
HEPATIC ENZYME INCREASED	1/101 (1%)	1	0/103 (0%)	0
WEIGHT INCREASED	1/101 (1%)	1	0/103 (0%)	0
Metabolism and nutrition disorders
ANOREXIA	2/101 (2%)	2	3/103 (2.9%)	3
DECREASED APPETITE	2/101 (2%)	2	1/103 (1%)	1
DIABETES MELLITUS	1/101 (1%)	1	1/103 (1%)	2
FLUID RETENTION	1/101 (1%)	1	0/103 (0%)	0
HYPERGLYCAEMIA	1/101 (1%)	1	0/103 (0%)	0
HYPERURICAEMIA	1/101 (1%)	1	0/103 (0%)	0
HYPOALBUMINAEMIA	0/101 (0%)	0	1/103 (1%)	1
HYPOCALCAEMIA	0/101 (0%)	0	1/103 (1%)	1
VITAMIN D DEFICIENCY	1/101 (1%)	1	0/103 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	10/101 (9.9%)	14	8/103 (7.8%)	8
BONE PAIN	14/101 (13.9%)	19	10/103 (9.7%)	23
MYALGIA	3/101 (3%)	3	9/103 (8.7%)	10
BACK PAIN	4/101 (4%)	4	3/103 (2.9%)	3
MUSCULOSKELETAL PAIN	2/101 (2%)	3	2/103 (1.9%)	2
MUSCLE SPASMS	1/101 (1%)	1	2/103 (1.9%)	3
PAIN IN EXTREMITY	0/101 (0%)	0	3/103 (2.9%)	4
JOINT STIFFNESS	0/101 (0%)	0	1/103 (1%)	3
MUSCULOSKELETAL CHEST PAIN	0/101 (0%)	0	3/103 (2.9%)	3
OSTEOARTHRITIS	1/101 (1%)	2	1/103 (1%)	1
BURSITIS	0/101 (0%)	0	1/103 (1%)	1
GROIN PAIN	1/101 (1%)	1	0/103 (0%)	0
MUSCLE CONTRACTURE	1/101 (1%)	1	0/103 (0%)	0
SYMPATHETIC POSTERIOR CERVICAL SYNDROME	1/101 (1%)	1	0/103 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	1/101 (1%)	1	0/103 (0%)	0
INFECTED NEOPLASM	1/101 (1%)	1	0/103 (0%)	0
METASTASES TO CENTRAL NERVOUS SYSTEM	0/101 (0%)	0	1/103 (1%)	1
TUMOUR PAIN	1/101 (1%)	1	0/103 (0%)	0
Nervous system disorders
DIZZINESS	4/101 (4%)	4	6/103 (5.8%)	6
HEADACHE	4/101 (4%)	26	13/103 (12.6%)	16
NEURALGIA	1/101 (1%)	1	2/103 (1.9%)	2
DYSGEUSIA	0/101 (0%)	0	2/103 (1.9%)	2
LETHARGY	2/101 (2%)	2	0/103 (0%)	0
SOMNOLENCE	0/101 (0%)	0	2/103 (1.9%)	2
CEREBRAL ISCHAEMIA	0/101 (0%)	0	1/103 (1%)	1
DIABETIC NEUROPATHY	1/101 (1%)	1	0/103 (0%)	0
DISTURBANCE IN ATTENTION	0/101 (0%)	0	1/103 (1%)	1
MEMORY IMPAIRMENT	0/101 (0%)	0	1/103 (1%)	1
PARKINSON'S DISEASE	0/101 (0%)	0	1/103 (1%)	1
PAROSMIA	0/101 (0%)	0	1/103 (1%)	1
SYNCOPE	0/101 (0%)	0	1/103 (1%)	1
VITH NERVE PARALYSIS	1/101 (1%)	1	0/103 (0%)	0
Psychiatric disorders
DEPRESSION	2/101 (2%)	2	4/103 (3.9%)	4
ANXIETY	3/101 (3%)	3	2/103 (1.9%)	2
INSOMNIA	2/101 (2%)	2	1/103 (1%)	1
DEPRESSED MOOD	2/101 (2%)	2	0/103 (0%)	0
CRYING	0/101 (0%)	0	1/103 (1%)	1
LIBIDO DECREASED	0/101 (0%)	0	1/103 (1%)	1
NEUROSIS	0/101 (0%)	0	1/103 (1%)	1
Renal and urinary disorders
DYSURIA	0/101 (0%)	0	2/103 (1.9%)	2
URINE ODOUR ABNORMAL	1/101 (1%)	1	0/103 (0%)	0
HAEMATURIA	0/101 (0%)	0	1/103 (1%)	1
NEPHROLITHIASIS	0/101 (0%)	0	1/103 (1%)	1
Reproductive system and breast disorders
BREAST PAIN	1/101 (1%)	1	2/103 (1.9%)	2
VULVOVAGINAL DRYNESS	0/101 (0%)	0	2/103 (1.9%)	2
BREAST HAEMORRHAGE	1/101 (1%)	1	0/103 (0%)	0
BREAST TENDERNESS	0/101 (0%)	0	1/103 (1%)	1
CERVICAL POLYP	0/101 (0%)	0	1/103 (1%)	1
DYSPAREUNIA	0/101 (0%)	0	1/103 (1%)	1
GENITAL DISCHARGE	1/101 (1%)	1	0/103 (0%)	0
GENITAL RASH	0/101 (0%)	0	1/103 (1%)	1
METRORRHAGIA	1/101 (1%)	1	0/103 (0%)	0
Respiratory, thoracic and mediastinal disorders
COUGH	5/101 (5%)	6	8/103 (7.8%)	9
DYSPNOEA	7/101 (6.9%)	8	7/103 (6.8%)	7
DYSPHONIA	1/101 (1%)	1	5/103 (4.9%)	5
PHARYNGOLARYNGEAL PAIN	2/101 (2%)	2	1/103 (1%)	1
EPISTAXIS	1/101 (1%)	1	1/103 (1%)	1
NASAL CONGESTION	1/101 (1%)	1	1/103 (1%)	1
ALLERGIC SINUSITIS	1/101 (1%)	1	0/103 (0%)	0
BRONCHOSPASM	1/101 (1%)	1	0/103 (0%)	0
DYSPNOEA EXERTIONAL	0/101 (0%)	0	1/103 (1%)	1
LARYNGEAL DISORDER	0/101 (0%)	0	1/103 (1%)	1
LUNG INFILTRATION	0/101 (0%)	0	1/103 (1%)	1
NASAL DRYNESS	0/101 (0%)	0	1/103 (1%)	1
PLEURAL EFFUSION	0/101 (0%)	0	1/103 (1%)	1
RALES	1/101 (1%)	1	0/103 (0%)	0
UPPER RESPIRATORY TRACT INFLAMMATION	0/101 (0%)	0	1/103 (1%)	1
Skin and subcutaneous tissue disorders
ALOPECIA	3/101 (3%)	3	2/103 (1.9%)	2
RASH	2/101 (2%)	2	1/103 (1%)	3
HYPERHIDROSIS	4/101 (4%)	4	0/103 (0%)	0
DERMATITIS CONTACT	2/101 (2%)	3	0/103 (0%)	0
PRURITUS	2/101 (2%)	2	1/103 (1%)	1
DRY SKIN	1/101 (1%)	1	1/103 (1%)	1
NIGHT SWEATS	1/101 (1%)	1	1/103 (1%)	1
COLD SWEAT	1/101 (1%)	1	0/103 (0%)	0
DERMATITIS ALLERGIC	0/101 (0%)	0	1/103 (1%)	1
ECZEMA	0/101 (0%)	0	1/103 (1%)	1
SCAR	1/101 (1%)	1	0/103 (0%)	0
SUBCUTANEOUS NODULE	1/101 (1%)	1	0/103 (0%)	0
Vascular disorders
HOT FLUSH	8/101 (7.9%)	8	14/103 (13.6%)	15
HYPERTENSION	6/101 (5.9%)	6	2/103 (1.9%)	5
HAEMATOMA	2/101 (2%)	2	0/103 (0%)	0
HYPERAEMIA	2/101 (2%)	2	0/103 (0%)	0
PHLEBITIS	1/101 (1%)	1	1/103 (1%)	1
HYPOTENSION	1/101 (1%)	1	0/103 (0%)	0

Limitations/Caveats

One patient in the ITT population was randomized to Fulvestrant 500 but did not receive drug and was excluded from the safety population. Hence, the safety population for Fulvestrant contained 101 patients.

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.