Fulvestrant (Faslodex) + Anastrozole (Arimidex) vs Anastrozole

• Sponsor: Spanish Breast Cancer Research Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00543127
• Collaborator: AstraZeneca (Industry)
• Enrollment: 870
• Locations: 53
• Arms: 2
• Actual Duration (Months): 104
• Patients Per Site: 16.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Postmenopausal women with hormone receptor positive and negative Her2 tumours.

Before randomization, the patients will be stratified according to the center, positive nodes (0 vs. 1-3 vs. ≥4), previous chemotherapy (yes vs no) and hormonal receptors status.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Fulvestrant; Drug: Anastrozole	Phase 3

Detailed Description

It is expected that disease-free survival for patients receiving Anastrozole alone for 5 years will be up to 90%. An increase of 3% in disease-free survival (DFS) is expected in the arm of Fulvestrant plus Anastrozole, i.e a DFS of up to 93%. They will be required 1358 patients per treatment group (i.e, 2716 patients in total) to give 80% power, alfa bilateral 0.05, and OR 0.6888. Assuming 5% screening failures 2852 patients are required to enter the study. In Jun-2010 the recruitment was stopped due to lack of support of the financier based on the result of Faslodex® and Arimidex® in Combination Trial (FACT-trial), comparing Fulvestrant + Anastrozole vs Anastrozole alone in 1st relapse showed no difference in time to progression at more than 40 months follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 870 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Trial Comparing Efficacy and Tolerance of Fulvestrant for 3 Years (y) Combined With Anastrozole 5 y Versus Anastrozole 5 y as Adjuvant Hormonotherapy in Postmenopausal With Early Breast Cancer and Positive Hormone Receptors
• Actual Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fulvestrant + Anastrozole Fulvestrant loading dose regimen will consist of two 5 ml intramuscular injections on day 0 (500 mg), 250 mg single injection on days 14 and 28, and 250 mg single injection every 28 days thereafter for 3 years plus Anastrozole 1 mg PO once daily for 5 years	Drug: Fulvestrant; 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.; Other Names: Faslodex ; Drug: Anastrozole; 1 mg oral Anastrozole per day during 5 years.; Other Names: Arimidex
Active Comparator: Anastrozole Anastrozole 1 mg will be administered orally as one tablet daily for 5 years.	Drug: Anastrozole; 1 mg oral Anastrozole per day during 5 years.; Other Names: Arimidex

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival (DFS) Events [Up to 5 years]

   Disease-free survival (DFS) has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. DFS event is defined as the evidence of local and/or distant recurrence, new primary breast tumour, or death from any cause.

Secondary Outcome Measures

1. Breast Cancer Specific Survival (BCsS) Events [Up to 5 years]

   BCsS events has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to BCsS in patients treated with anastrozole for 5 years. BCsS event is defined as the death from breast cancer.

2. Overall Survival (OS) Event [Up to 5 years]

   OS event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. OS event is defined as the death from any cause.

3. Time to Recurrence (TR) Event [Up to 5 years]

   TR event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. TR event is defined as the evidence of breast cancer recurrence (local and/or distant recurrence of breast cancer, does not include second primary malignancies or deaths from any cause).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Histological documentation of breast cancer.

2. Stage I, II, IIIA and IIIC* invasive breast cancer. One of these two characteristics must be fulfilled:

• N+

• T > 1cm *Eligible patients T1-T3 and pN3a (patients with metastasis in infraclavicular nodes would not be eligible)

1. Local treatment with curative intention:

• mastectomy or tumour excision with free margins + radiotherapy

• axillary lymphadenectomy or sentinel node biopsy

1. Positive hormone receptors (Estrogen Receptor [ER]+ and/or Progesterone Receptor [PR]+) in primary tumour tissue as measured by a central laboratory

2. Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, defined as immunohistochemistry (IHC) 0 or 1+ or negative fluorescence in situ hybridization (FISH) (in the event of IHC 2+ or 3+)

3. Postmenopausal women, defined as women meeting any of the following criteria:

• Age ≥ 60 years

• Age ≥ 45 years with amenorrhea ≥ 12 months in the moment of breast cancer diagnosis and an intact uterus

• Prior bilateral ovariectomy

• In case previous hysterectomy, follicle stimulating hormone (FSH) and estradiol levels within the postmenopausal range (using local laboratory ranges)* * In patients previously treated with a luteinizing hormone releasing hormone (LH-RH) analogue, the last extended release formulation should have been administered more than 6 months before randomisation, and menses must not have reappeared.

1. A World Health Organization (WHO) performance status of 0, 1, or 2.

2. Age > 18 years

Exclusion criteria:

1. Presence of metastatic disease or bilateral invasive cancer

2. ER and Progesterone Receptor (PR) negative breast cancer

3. HER2-positive breast cancer, defined as FISH+

4. Treatment with a non-approved or experimental drug within 4 months of randomisation

5. Current malignancy or previous malignancy in the past 5 years (other that breast cancer or basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)

6. Pregnant or nursing patients

7. Any of the following laboratory values within 3 months of randomisation:

• Platelets < 100 x 109/L

• Total bilirubin > 1.5 x Upper limit of reference range (ULRR)**

** Patients with documented Gilbert syndrome may be included in this trial

• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 2.5 x ULRR

• A history of:

• hemorrhagic diathesis (i.e. Disseminated Intravascular Coagulation [DIC], coagulation factor deficiency) or

• long-term anticoagulant treatment (except for anti-platelet aggregants and low-dose warfarin; see section 3.7)

1. A history of hypersensitivity to the active ingredient or inactive excipients of fulvestrant, aromatase inhibitors, or castor oil

2. Any concomitant severe disease advising against patient participation in the trial o that may jeopardize compliance with the trial protocol, such as uncontrolled heart disease, uncontrolled diabetes mellitus, or uncontrolled severe infections

3. Hormone replacement therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Virgen de Los Lirios	Alcoy	Alicante	Spain	03804
2	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
3	Hospital General Universitario de Elda	Elda	Alicante	Spain	03600
4	Hospital Usp San Jaime	Torrevieja	Alicante	Spain	03180
5	Hospital de Torrevieja Salud Ute	Torrevieja	Alicante	Spain	03186
6	Hospital San Agustín de Avilés	Avilés	Asturias	Spain	33400
7	Hospital Municipal de Badalona	Badalona	Barcelona	Spain	08911
8	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona	Spain	08916
9	Hospital General de Granollers	Granollers	Barcelona	Spain	08402
10	Institut Catalá D'Oncología L'Hospitalet	L'hospitalet de Llobregat	Barcelona	Spain	08907
11	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona	Spain	08208
12	Hospital Mutua de Terrassa	Terrassa	Barcelona	Spain	08221
13	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain	08227
14	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
15	Consorcio Hospitalario Provincial de Castellón	Castellón de La Plana	Castellón	Spain	12002
16	Hospital Donostia	Donostia-san Sebastián	Guipúzcoa	Spain	20014
17	Onkologikoa	Donostia-san Sebastián	Guipúzcoa	Spain	20014
18	Hospital de Barbastro	Barbastro	Huesca	Spain	22300
19	Complejo Hospitalario Universitario Insular-Materno Infantil	Las Palmas de Gran Canaria	LAS Palmas	Spain	35016
20	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid	Spain	28922
21	Hospital Universitario de Canarias	La Laguna	Santa CRUZ DE Tenerife	Spain	38320
22	Hospital Universitario de Valme	Dos Hermanas	Sevilla	Spain	41700
23	Hospital de Sagunto	Sagunto	Valencia	Spain	46520
24	Hospital Lluís Alcanyis	Xátiva	Valencia	Spain	46800
25	Hospital de Basurto	Bilbao	Vizcaya	Spain	48013
26	Complejo Hospitalario Universitario A Coruña	A Coruña		Spain	15006
27	Centro Oncológico de Galicia	A Coruña		Spain	15009
28	Complejo Hospitalario Torrecárdenas	Almería		Spain	04009
29	Hospital de La Santa Creu I Sant Pau	Barcelona		Spain	08025
30	Hospital Clinic I Provincial de Barcelona	Barcelona		Spain	08036
31	Hospital Universitario Puerta Del Mar	Cadiz		Spain	11009
32	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
33	HOSPITAL UNIVERSITARI DE GIRONA DR. JOSEP TRUETA (ICO de Girona)	Girona		Spain	17007
34	Hospital Universitario San Cecilio	Granada		Spain	18012
35	Hospital General Universitario de Guadalajara	Guadalajara		Spain	19002
36	Hospital Juan Ramón Jiménez	Huelva		Spain	21005
37	Complejo Hospitalario de Jaén	Jaén		Spain	23007
38	Hospital Universitario Arnau de Vilanova de Lleida	Lleida		Spain	25198
39	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
40	Hospital Universitario Ramón Y Cajal	Madrid		Spain	28034
41	Hospital Clínico Universitario San Carlos	Madrid		Spain	28040
42	CENTRO INTEGRAL ONCOLÓGICO CLARA CAMPAL (Hospital Madrid Norte Sanchinarro)	Madrid		Spain	28050
43	Hospital Clínico Universitario Virgen de La Victoria	Malaga		Spain	29010
44	Hospital Regional Universitario Carlos Haya	Malaga		Spain	29010
45	Hospital General Universitario Morales Meseguer	Murcia		Spain	30008
46	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz de Tenerife		Spain	38010
47	Hospital Universitario Virgen Del Rocío	Sevilla		Spain	41013
48	Hospital Virgen de La Salud	Toledo		Spain	45004
49	Instituto Valenciano de Oncología	Valencia		Spain	46009
50	Consorcio Hospital General Universitario de Valencia	Valencia		Spain	46014
51	Hospital Clínico Universitario de Valencia	Valencia		Spain	46015
52	Hospital Universitario Arnau de Vilanova de Valencia	Valencia		Spain	46015
53	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

• Spanish Breast Cancer Research Group
• AstraZeneca

Investigators

• Study Director: Study Director, Hospital General Universitario Gregorio Marañón
• Study Director: Study Director, Centro Oncológico de Galicia
• Study Director: Study Director, Hospitales Universitarios Virgen del Rocío

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Description Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Publications

None provided.

• Responsible Party: Spanish Breast Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00543127
• Other Study ID Numbers: GEICAM/2006-10
• First Posted: Oct 12, 2007
• Last Update Posted: Apr 5, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant; Anastrozole

Study Results

Participant Flow

Recruitment Details	870 patients were recruited, from them, 437 were randomized to Anastrozole (A) and 433 to A plus Fulvestrant (F), but 18 patients (3 in A arm and 15 in arm A+F) never received treatment.

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.
Period Title: Overall Study
STARTED	433	437
COMPLETED	303	350
NOT COMPLETED	130	87

Baseline Characteristics

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole	Total
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.	Total of all reporting groups
Overall Participants	433	437	870
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62	62
Sex: Female, Male (Count of Participants)
Female	433 100%	437 100%	870 100%
Male	0 0%	0 0%	0 0%
Breast Surgery (Count of Participants)
Conservative	303 70%	310 70.9%	613 70.5%
Mastectomy	130 30%	127 29.1%	257 29.5%
Axillary surgery (Count of Participants)
Axillary dissection	258 59.6%	281 64.3%	539 62%
Sentinel Node Biopsy	174 40.2%	155 35.5%	329 37.8%
Unknown	1 0.2%	1 0.2%	2 0.2%
Previous chemotherapy (Count of Participants)
Adjuvant	256 59.1%	261 59.7%	517 59.4%
Neoadjuvant	37 8.5%	34 7.8%	71 8.2%
Neoadjuvant + Adjuvant	3 0.7%	2 0.5%	5 0.6%
None	137 31.6%	140 32%	277 31.8%
Previous radiotherapy (Count of Participants)
YES	348 80.4%	347 79.4%	695 79.9%
NO	85 19.6%	90 20.6%	175 20.1%
Histopathologic type (Count of Participants)
Invasive Ductal Carcinoma	337 77.8%	346 79.2%	683 78.5%
Invasive Lobular Carcinoma	71 16.4%	71 16.2%	142 16.3%
Other	25 5.8%	20 4.6%	45 5.2%
Histologic grade (Count of Participants)
Grade 1	88 20.3%	82 18.8%	170 19.5%
Grade 2	216 49.9%	235 53.8%	451 51.8%
Grade 3	94 21.7%	83 19%	177 20.3%
Grade X	35 8.1%	37 8.5%	72 8.3%
Tumor size (cm) [Median (Full Range) ]
Median (Full Range) [cm]	2	2	2
Final diagnosis tumor size (Count of Participants)
T1	220 50.8%	243 55.6%	463 53.2%
T2	189 43.6%	179 41%	368 42.3%
T3-T4	22 5.1%	14 3.2%	36 4.1%
TX	2 0.5%	1 0.2%	3 0.3%
Nodal status (Count of Participants)
N0	214 49.4%	200 45.8%	414 47.6%
N1	157 36.3%	164 37.5%	321 36.9%
N2	42 9.7%	52 11.9%	94 10.8%
N3	14 3.2%	18 4.1%	32 3.7%
NX	6 1.4%	3 0.7%	9 1%

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival (DFS) Events
Description	Disease-free survival (DFS) has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. DFS event is defined as the evidence of local and/or distant recurrence, new primary breast tumour, or death from any cause.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Primary statistical analyses of the efficacy outcome variables will be based on an intent-to-treat (ITT) method and will include all randomised patients

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.
Measure Participants	433	437
Count of Participants [Participants]	49 11.3%	62 14.2%

2. Secondary Outcome

Title	Breast Cancer Specific Survival (BCsS) Events
Description	BCsS events has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to BCsS in patients treated with anastrozole for 5 years. BCsS event is defined as the death from breast cancer.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Analyses of the efficacy outcome variables will be based on an intent-to-treat (ITT) method and will include all randomised patients.

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.
Measure Participants	433	437
Count of Participants [Participants]	17 3.9%	18 4.1%

3. Secondary Outcome

Title	Overall Survival (OS) Event
Description	OS event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. OS event is defined as the death from any cause.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Statistical analyses of the efficacy outcome variables will be based on an intent-to-treat (ITT) method and will include all randomised patients.

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.
Measure Participants	433	437
Count of Participants [Participants]	28 6.5%	34 7.8%

4. Secondary Outcome

Title	Time to Recurrence (TR) Event
Description	TR event has been evaluated in patients treated with Fulvestrant for 3 years and Anastrozole for 5 years as compared to DFS in patients treated with anastrozole for 5 years. TR event is defined as the evidence of breast cancer recurrence (local and/or distant recurrence of breast cancer, does not include second primary malignancies or deaths from any cause).
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fulvestrant + Anastrozole	Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.	Anastrozole: 1 mg oral Anastrozole per day during 5 years.
Measure Participants	433	437
Count of Participants [Participants]	36 8.3%	46 10.5%

Adverse Events

Time Frame	Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) will be recorded from the date informed consent is signed, during the treatment period, and for up to 8 weeks after the last injection in patients randomised to fulvestrant if this patient does not continue with anastrozole, or up to 30 days after the last tablet when this is the last study treatment received by the patient.
Adverse Event Reporting Description	These Adverse Events are by patient (not per cycle). Only grades 2, 3 and 4 are specified.
Arm/Group Title	Fulvestrant + Anastrozole		Anastrozole
Arm/Group Description	Fulvestrant + Anastrozole: 500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral Anastrozole per day during 5 years.		Anastrozole: 1 mg oral Anastrozole per day during 5 years.
All Cause Mortality
	Fulvestrant + Anastrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fulvestrant + Anastrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/415 (9.6%)		61/437 (14%)
Blood and lymphatic system disorders
Hemoglobin	0/415 (0%)	0	1/437 (0.2%)	1
chronic lymphocytic leukemia	0/415 (0%)	0	1/437 (0.2%)	1
lymphoblastic leukemia	0/415 (0%)	0	1/437 (0.2%)	1
Thrombotic microangiopathy	0/415 (0%)	0	1/437 (0.2%)	1
Hematoma	0/415 (0%)	0	1/437 (0.2%)	1
Hemorrhage, CNS	1/415 (0.2%)	1	0/437 (0%)	0
Hemorrhage, gi - colon	0/415 (0%)	0	1/437 (0.2%)	1
Hemorrhage, gi - stomach	0/415 (0%)	0	1/437 (0.2%)	1
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	0/415 (0%)	0	1/437 (0.2%)	1
Cardiac disorders
Conduction abnormality/atrioventricular heart block - av block-second degree mobitz type ii	0/415 (0%)	0	1/437 (0.2%)	1
Supraventricular and nodal arrhythmia - atrial fibrillation	0/415 (0%)	0	1/437 (0.2%)	1
Supraventricular and nodal arrhythmia - sinus tachycardia	0/415 (0%)	0	1/437 (0.2%)	1
Cardiac ischemia/infarction	2/415 (0.5%)	2	1/437 (0.2%)	1
Angor	0/415 (0%)	0	1/437 (0.2%)	1
dilated cardiomyopathy	1/415 (0.2%)	1	0/437 (0%)	0
Pericarditis	0/415 (0%)	0	1/437 (0.2%)	1
Valvular heart disease	0/415 (0%)	0	2/437 (0.5%)	2
Endocrine disorders
goitre	2/415 (0.5%)	2	0/437 (0%)	0
Gastrointestinal disorders
Colitis	0/415 (0%)	0	1/437 (0.2%)	1
Diarrhea	0/415 (0%)	0	1/437 (0.2%)	1
Gastritis	1/415 (0.2%)	1	0/437 (0%)	0
Ileus, gi (functional obstruction of bowel, i.e., neuroconstipation)	1/415 (0.2%)	1	0/437 (0%)	0
Nausea	0/415 (0%)	0	1/437 (0.2%)	1
Colon cancer	3/415 (0.7%)	3	3/437 (0.7%)	3
Inguinal Hernia	1/415 (0.2%)	1	0/437 (0%)	0
Rectum cancer	1/415 (0.2%)	1	0/437 (0%)	0
Transverse colon adenocarcinoma	0/415 (0%)	0	1/437 (0.2%)	1
Perforation, gi - appendix	0/415 (0%)	0	1/437 (0.2%)	1
Ulcer, gi - duodenum	1/415 (0.2%)	1	0/437 (0%)	0
Vomiting	0/415 (0%)	0	1/437 (0.2%)	1
Gastrointestinal abdomen nos pain	0/415 (0%)	0	2/437 (0.5%)	2
Gastric difuse	1/415 (0.2%)	1	0/437 (0%)	0
General disorders
Flu-like syndrome	0/415 (0%)	0	1/437 (0.2%)	1
Hepatobiliary disorders
Cholecystitis	2/415 (0.5%)	2	1/437 (0.2%)	1
Liver dysfunction/failure (clinical)	0/415 (0%)	0	1/437 (0.2%)	1
acute hepatitis	1/415 (0.2%)	1	0/437 (0%)	0
cholelithiasis	1/415 (0.2%)	1	3/437 (0.7%)	3
pancreas cancer	1/415 (0.2%)	1	0/437 (0%)	0
Pancreatitis	0/415 (0%)	0	1/437 (0.2%)	1
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/415 (0.2%)	1	0/437 (0%)	0
Infections and infestations
Infection (documented clinically or microbiologically) with grade 3 or 4 neutrophils (anc <1.0 x 109	0/415 (0%)	0	1/437 (0.2%)	1
Infection with normal ANC or grade 1 or 2 neutrophils dermatology/skin skin (cellulitis)	1/415 (0.2%)	1	1/437 (0.2%)	1
Infection with normal ANC or grade 1 or 2 neutrophils - pulmonary/upper respiratory bronchus	1/415 (0.2%)	1	0/437 (0%)	0
Infection with normal ANC or grade 1 or 2 neutrophils - pulmonary/upper respiratory lung (pneumonia)	3/415 (0.7%)	3	0/437 (0%)	0
Infection with normal ANC or grade 1 or 2 neutrophils - pulmonary/upper respiratory upper airway nos	0/415 (0%)	0	1/437 (0.2%)	1
Infection with normal ANC or grade 1 or 2 neutrophils - sexual/reproductive function vagina and vulv	1/415 (0.2%)	1	0/437 (0%)	0
Infection with unknown ANC - cardiovascular heart (endocarditis)	0/415 (0%)	0	1/437 (0.2%)	1
Infection with unknown ANC - gastrointestinal appendix	1/415 (0.2%)	1	1/437 (0.2%)	1
Infection with unknown ANC - gastrointestinal dental-tooth	0/415 (0%)	0	1/437 (0.2%)	1
Infection with unknown ANC - pulmonary/upper respiratory lung (pneumonia)	1/415 (0.2%)	1	2/437 (0.5%)	2
Infection with unknown ANC - renal/genitourinary urinary tract nos	0/415 (0%)	0	1/437 (0.2%)	1
Infection with normal ANC or grade 1 or 2 neutrophils - renal/genitourinary kidney	0/415 (0%)	0	1/437 (0.2%)	1
Infection with normal ANC or grade 1 or 2 neutrophils - renal/genitourinary urinary tract nos	0/415 (0%)	0	1/437 (0.2%)	1
Musculoskeletal and connective tissue disorders
Fracture	3/415 (0.7%)	3	5/437 (1.1%)	5
arthrosis	1/415 (0.2%)	1	1/437 (0.2%)	1
Synovial cyst	0/415 (0%)	0	1/437 (0.2%)	1
Other: tendon rupture	1/415 (0.2%)	1	0/437 (0%)	0
Musculoskeletal back pain	1/415 (0.2%)	1	1/437 (0.2%)	1
Musculoskeletal bone pain	1/415 (0.2%)	1	1/437 (0.2%)	1
Musculoskeletal joint pain	1/415 (0.2%)	1	1/437 (0.2%)	1
Musculoskeletal neck pain	0/415 (0%)	0	1/437 (0.2%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/415 (0.2%)	1	4/437 (0.9%)	4
Neuropathy: craneal - cn vi downward, inward movement of eye	0/415 (0%)	0	1/437 (0.2%)	1
glioblastoma multiforme	1/415 (0.2%)	1	0/437 (0%)	0
Meningioma	0/415 (0%)	0	1/437 (0.2%)	1
Renal and urinary disorders
Cystocele	0/415 (0%)	0	1/437 (0.2%)	1
Nephrolithiasis	0/415 (0%)	0	1/437 (0.2%)	1
Renal failure	0/415 (0%)	0	2/437 (0.5%)	2
Secondary malignancy - possiby related to cancer treatment, specify: kidney cancer	1/415 (0.2%)	1	0/437 (0%)	0
Reproductive system and breast disorders
Secondary malignancy - possiby related to cancer treatment, specify: uterine cervix cancer	0/415 (0%)	0	1/437 (0.2%)	1
Breast cancer	1/415 (0.2%)	1	0/437 (0%)	0
Breast nodule	1/415 (0.2%)	1	0/437 (0%)	0
Endometrial adenocarcinoma	0/415 (0%)	0	1/437 (0.2%)	1
Microcalcification in breast	0/415 (0%)	0	1/437 (0.2%)	1
Uterine polyp	1/415 (0.2%)	1	0/437 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary/upper respiratory chest/thorax nos pain	0/415 (0%)	0	1/437 (0.2%)	1
Dyspnea (shortness of breath)	0/415 (0%)	0	1/437 (0.2%)	1
Lung cancer	1/415 (0.2%)	1	0/437 (0%)	0
Pleural effusion (non-malignant)	0/415 (0%)	0	1/437 (0.2%)	1
Pneumonitis/pulmonary infiltrates	1/415 (0.2%)	1	1/437 (0.2%)	1
Skin and subcutaneous tissue disorders
Induration/fibrosis (skin and subcutaneous tissue)	0/415 (0%)	0	1/437 (0.2%)	1
Injection site reaction/extravasation changes	1/415 (0.2%)	1	0/437 (0%)	0
melanoma	1/415 (0.2%)	1	0/437 (0%)	0
squamous cell carcinoma	1/415 (0.2%)	1	0/437 (0%)	0
t-cell lymphoma	0/415 (0%)	0	1/437 (0.2%)	1
Social circumstances
Traffic accident	0/415 (0%)	0	1/437 (0.2%)	1
Vascular disorders
Thrombosis/embolism (vascular access-related)	0/415 (0%)	0	3/437 (0.7%)	3
Other (Not Including Serious) Adverse Events
	Fulvestrant + Anastrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/415 (46.3%)		197/437 (45.1%)
Cardiac disorders
Hypertension	41/415 (9.9%)	41	58/437 (13.3%)	58
Endocrine disorders
Hot flashes/flushes	23/415 (5.5%)	23	18/437 (4.1%)	18
General disorders
Fatigue (asthenia, lethargy, malaise)	49/415 (11.8%)	49	23/437 (5.3%)	23
Weight gain	39/415 (9.4%)	39	31/437 (7.1%)	31
Weight loss	37/415 (8.9%)	37	41/437 (9.4%)	41
Metabolism and nutrition disorders
Cholesterol, serum-high (hypercholesterolemia)	21/415 (5.1%)	21	23/437 (5.3%)	23
LDL-cholesterol high	22/415 (5.3%)	22	41/437 (9.4%)	41
Musculoskeletal and connective tissue disorders
Musculoskeletal bone pain	39/415 (9.4%)	39	34/437 (7.8%)	34
Musculoskeletal joint pain	83/415 (20%)	83	81/437 (18.5%)	81

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.