S0226 Anastrozole With or Without Fulvestrant as First-Line Therapy in Postmenopausal Women With Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00075764

Recruitment Status : Completed

First Posted : January 13, 2004

Results First Posted : April 4, 2017

Last Update Posted : January 13, 2021

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Sponsor:

Collaborators:

National Cancer Institute (NCI)

NCIC Clinical Trials Group

Information provided by (Responsible Party):

SWOG Cancer Research Network

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Breast Cancer
Interventions	Drug: anastrozole Drug: fulvestrant
Enrollment	695

Participant Flow

Recruitment Details

707 Patients underwent randomization. 12 were excluded: 9 did not have metastatic disease, 1 had previous chemotherapy, 1 was estrogen-receptor and progesterone-receptor negative, 1 did not undergo chest imaging. In addition, 1 patient withdrew consent.

694 patients were included in the analysis.

Pre-assignment Details


Arm/Group Title	Arm I Anastrozole	Arm II Anastrozole and Fulvestrant
Arm/Group Description	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description	Patients receive oral anastrozole once daily on days 1-28. anastrozole: Given orally	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. anastrozole: Given orally fulvestrant: Given intramuscularly
Period Title: Overall Study
Started	345	349
Completed	0	0
Not Completed	345	349
Reason Not Completed
Adverse Event	5	12
Death	4	8
Withdrawal by Subject	28	18
Progression	269	274
Still on treatment	8	15
Delinquent	4	2
Not protocol specified	27	19
Under review	0	1

Baseline Characteristics

Arm/Group Title		Arm I Anastrozole	Arm II Anastrozole and Fulvestrant	Total
Arm/Group Description		Patients receive oral anastrozole o...	Patients receive oral anastrozole a...	Total of all reporting groups
Arm/Group Description		Patients receive oral anastrozole once daily on days 1-28. anastrozole: Given orally	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. anastrozole: Given orally fulvestrant: Given intramuscularly	Total of all reporting groups
Overall Number of Baseline Participants		345	349	694
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	345 participants	349 participants	694 participants
		65 (36 to 91)	65 (27 to 92)	65 (27 to 92)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	345 participants	349 participants	694 participants
	Female	345 100.0%	349 100.0%	694 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Prior adjuvant tamoxifen Measure Type: Number Unit of measure: Participants
Yes	Number Analyzed	345 participants	349 participants	694 participants
Yes		139	141	280
No	Number Analyzed	345 participants	349 participants	694 participants
No		206	208	414
Prior adjuvant chemotherapy Measure Type: Number Unit of measure: Participants
Yes	Number Analyzed	345 participants	349 participants	694 participants
Yes		103	129	232
No	Number Analyzed	345 participants	349 participants	694 participants
No		242	220	462
Measurable disease Measure Type: Number Unit of measure: Participants
Yes	Number Analyzed	345 participants	349 participants	694 participants
Yes		188	188	376
No	Number Analyzed	345 participants	349 participants	694 participants
No		157	161	318
Disease site Measure Type: Number Unit of measure: Participants
Bone only	Number Analyzed	345 participants	349 participants	694 participants
Bone only		76	75	151
Visceral	Number Analyzed	345 participants	349 participants	694 participants
Visceral		167	181	348
Nonvisceral	Number Analyzed	345 participants	349 participants	694 participants
Nonvisceral		102	93	195
Time between diagnosis of primary and metastatic disease ^[1] Measure Type: Number Unit of measure: Participants
None	Number Analyzed	337 participants	339 participants	676 participants
None		141	122	263
3 mo to < 5 yr	Number Analyzed	337 participants	339 participants	676 participants
3 mo to < 5 yr		40	47	87
5 to < 10 yr	Number Analyzed	337 participants	339 participants	676 participants
5 to < 10 yr		68	66	134
>= 10 yr	Number Analyzed	337 participants	339 participants	676 participants
>= 10 yr		88	104	192
		[1] Measure Analysis Population Description: Only patients with non missing value of time between diagnosis of primary and metastatic disease will be included.
HER2 status ^[1] [2] Measure Type: Number Unit of measure: Participants
Positive	Number Analyzed	295 participants	297 participants	592 participants
Positive		25	31	56
Negative	Number Analyzed	295 participants	297 participants	592 participants
Negative		270	266	536
		[1] Measure Description: HER2 denotes human epidermal growth factor receptor type 2. [2] Measure Analysis Population Description: Only patients with available HER2 status data will be included in the analysis.

Outcome Measures

1.Primary Outcome


Title	Time to Tumor Progression
Description	Progression is defined using Response Evaluation Criteria In Solid Tum...
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. From date of randomization to time of first documentation of progression, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression free are considered at last date of contact.
Time Frame	Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I Anastrozole	Arm II Anastrozole and Fulvestrant
Arm/Group Description:	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description:	Patients receive oral anastrozole once daily on days 1-28. anastrozole: Given orally	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. anastrozole: Given orally fulvestrant: Given intramuscularly
Overall Number of Participants Analyzed	345	349
Median (95% Confidence Interval) Unit of Measure: months
	13.5 (12.1 to 15.1)	15.0 (13.2 to 18.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Anastrozole, Arm II Anastrozole and Fulvestrant
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.007
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Two-sided stratified log-rank test

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95% 0.68 to 0.94
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks).
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0...
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable, Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Clinical Benefit = CR + PR + Stable >= 24 weeks
Time Frame	Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I Anastrozole	Arm II Anastrozole and Fulvestrant
Arm/Group Description:	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description:	Patients receive oral anastrozole once daily on days 1-28. anastrozole: Given orally	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. anastrozole: Given orally fulvestrant: Given intramuscularly
Overall Number of Participants Analyzed	345	349
Measure Type: Number Unit of Measure: percentage of participants
	70	73

3.Secondary Outcome


Title	Overall Survival
Description	From date of randomization to date of death due to any cause. Patients...
Description	From date of randomization to date of death due to any cause. Patients last known to be alive are censored at last date of contact.
Time Frame	Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm I Anastrozole	Arm II Anastrozole and Fulvestrant
Arm/Group Description:	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description:	Patients receive oral anastrozole once daily on days 1-28. anastrozole: Given orally	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses. anastrozole: Given orally fulvestrant: Given intramuscularly
Overall Number of Participants Analyzed	345	349
Median (95% Confidence Interval) Unit of Measure: months
	41.3 (37.2 to 45.0)	47.7 (43.4 to 55.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I Anastrozole, Arm II Anastrozole and Fulvestrant
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.049
	Comments	[Not Specified]
	Method	Log Rank
	Comments	A log-rank test, stratified according to prior or no prior tamoxifen therapy.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95% 0.65 to 1.00
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. Fo...
Description	Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. For each patient, worst grade of each event type is reported. Grade3 (Severe), Grade4 (Life-threatening), Grade 5 (Fatal)
Time Frame	Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment.

Outcome Measure Data

Analysis Population Description

Eligible patients who had received the protocol treatments were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.


Arm/Group Title	Arm I Anastrozole	Arm II Anastrozole and Fulvestrant
Arm/Group Description:	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description:	Patients receive oral anastrozole once daily on days 1-28	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1 , 14, and 28 during course 1 and then on day 28 of the subsequent courses.
Overall Number of Participants Analyzed	337	348
Measure Type: Number Unit of Measure: Participants
ALT, SGPT (serum glutamic pyruvic transaminase)	1	1
AST, SGOT	3	1
Albumin, serum-low (hypoalbuminemia)	1	1
Alkaline phosphatase	1	0
Anorexia	0	1
Bilirubin (hyperbilirubinemia)	1	0
CNS cerebrovascular ischemia	0	2
Calcium, serum-high (hypercalcemia)	1	0
Cataract	1	1
Confusion	0	1
Constipation	1	1
Dehydration	1	1
Diarrhea	2	1
Dizziness	1	2
Dyspnea (shortness of breath)	1	1
Edema: limb	1	1
Fatigue (asthenia, lethargy, malaise)	7	9
Febrile neutropenia	1	0
Fracture	1	2
Glucose, serum-high (hyperglycemia)	1	2
Hemoglobin	1	3
Hemolysis	1	1
Hot flashes/flushes	2	7
Hypertension	2	1
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	1	0
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	1	1
Infection with unknown ANC - Urinary tract NOS	0	2
Insomnia	0	1
Joint-effusion	0	2
Leukocytes (total WBC)	0	1
Lymphopenia	3	3
Memory impairment	1	0
Mood alteration - agitation	0	1
Mood alteration - anxiety	1	0
Mood alteration - depression	0	3
Mucositis/stomatitis (functional/symp) - Pharynx	1	0
Muscle weakness, not d/t neuropathy - body/general	1	0
Nausea	3	1
Neurology-Other (Specify)	1	0
Neuropathy: sensory	1	0
Neutrophils/granulocytes (ANC/AGC)	0	2
Pain - Abdomen NOS	1	2
Pain - Back	5	7
Pain - Bone	1	1
Pain - Breast	1	0
Pain - Buttock	1	0
Pain - Chest wall	0	1
Pain - Chest/thorax NOS	1	1
Pain - Extremity-limb	0	3
Pain - Head/headache	1	0
Pain - Joint	5	7
Pain - Muscle	3	0
Pain - Neck	0	1
Pain - Pelvis	0	3
Pain-Other (Specify)	2	1
Platelets	2	2
Rash/desquamation	1	1
Sodium, serum-low (hyponatremia)	0	1
Speech impairment (e.g., dysphasia or aphasia)	1	0
Sudden death	0	1
Syncope (fainting)	0	1
Thrombosis/embolism (vascular access-related)	3	1
Thrombosis/thrombus/embolism	6	7
Tinnitus	0	1
Tumor flare	0	2
Urticaria (hives, welts, wheals)	0	1
Vomiting	3	2
Weight gain	0	1

Adverse Events

Time Frame	Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment.
Adverse Event Reporting Description	Eligible patients who had received the protocol treatments and who were evaluable for adverse event assessment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.

Arm/Group Title	Anastrozole	Anastrozole & Fulvestrant
Arm/Group Description	Patients receive oral anastrozole o...	Patients receive oral anastrozole a...
Arm/Group Description	Patients receive oral anastrozole once daily on days 1-28	Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1 , 14, and 28 during course 1 and then on day 28 of the subsequent courses.
All-Cause Mortality
	Anastrozole	Anastrozole & Fulvestrant
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Anastrozole	Anastrozole & Fulvestrant
	Affected / at Risk (%)	Affected / at Risk (%)
Total	21/337 (6.23%)	48/348 (13.79%)
Blood and lymphatic system disorders
Blood/Bone Marrow-Other ^† 1	0/337 (0.00%)	1/348 (0.29%)
Febrile neutropenia ^† 1	0/337 (0.00%)	1/348 (0.29%)
Hemoglobin ^† 1	2/337 (0.59%)	1/348 (0.29%)
Cardiac disorders
Atrioventricular block - 2nd degree Mobitz Type II ^† 1	0/337 (0.00%)	1/348 (0.29%)
Cardiac-ischemia/infarction ^† 1	1/337 (0.30%)	2/348 (0.57%)
Left ventricular diastolic dysfunction ^† 1	0/337 (0.00%)	1/348 (0.29%)
Left ventricular systolic dysfunction ^† 1	1/337 (0.30%)	0/348 (0.00%)
Restrictive cardiomyopathy ^† 1	1/337 (0.30%)	0/348 (0.00%)
Eye disorders
Dry eye syndrome ^† 1	0/337 (0.00%)	1/348 (0.29%)
Gastrointestinal disorders
Constipation ^† 1	0/337 (0.00%)	3/348 (0.86%)
Diarrhea ^† 1	1/337 (0.30%)	1/348 (0.29%)
Ileus, GI (functional obstruction of bowel) ^† 1	0/337 (0.00%)	2/348 (0.57%)
Nausea ^† 1	0/337 (0.00%)	1/348 (0.29%)
Obstruction, GI - Ileum ^† 1	0/337 (0.00%)	1/348 (0.29%)
Obstruction, GI - Small bowel NOS ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pain - Abdomen NOS ^† 1	0/337 (0.00%)	2/348 (0.57%)
Perforation, GI - Colon ^† 1	0/337 (0.00%)	2/348 (0.57%)
Vomiting ^† 1	2/337 (0.59%)	1/348 (0.29%)
General disorders
Death not associated with CTCAE term - Death NOS ^† 1	1/337 (0.30%)	1/348 (0.29%)
Fatigue (asthenia, lethargy, malaise) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pain - Chest/thorax NOS ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pain-Other ^† 1	0/337 (0.00%)	1/348 (0.29%)
Sudden death ^† 1	0/337 (0.00%)	2/348 (0.57%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood ^† 1	0/337 (0.00%)	1/348 (0.29%)
Inf w/normal ANC or Gr 1-2 neutrophils - Bone ^† 1	0/337 (0.00%)	1/348 (0.29%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung ^† 1	1/337 (0.30%)	2/348 (0.57%)
Inf w/normal ANC or Gr 1-2 neutrophils - Pleura ^† 1	0/337 (0.00%)	1/348 (0.29%)
Inf w/normal ANC or Gr 1-2 neutrophils - Skin ^† 1	0/337 (0.00%)	1/348 (0.29%)
Inf w/normal ANC or Gr 1-2 neutrophils - UTI ^† 1	0/337 (0.00%)	3/348 (0.86%)
Infection with unknown ANC - Lung (pneumonia) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Infection with unknown ANC - Rectum ^† 1	0/337 (0.00%)	1/348 (0.29%)
Infection with unknown ANC - Urinary tract NOS ^† 1	0/337 (0.00%)	3/348 (0.86%)
Injury, poisoning and procedural complications
Fracture ^† 1	0/337 (0.00%)	5/348 (1.44%)
Investigations
Leukocytes (total WBC) ^† 1	1/337 (0.30%)	0/348 (0.00%)
Neutrophils/granulocytes (ANC/AGC) ^† 1	1/337 (0.30%)	1/348 (0.29%)
Platelets ^† 1	0/337 (0.00%)	1/348 (0.29%)
Metabolism and nutrition disorders
Anorexia ^† 1	0/337 (0.00%)	2/348 (0.57%)
Calcium, serum-low (hypocalcemia) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Dehydration ^† 1	0/337 (0.00%)	6/348 (1.72%)
Glucose, serum-high (hyperglycemia) ^† 1	0/337 (0.00%)	4/348 (1.15%)
Potassium, serum-low (hypokalemia) ^† 1	0/337 (0.00%)	2/348 (0.57%)
Sodium, serum-low (hyponatremia) ^† 1	0/337 (0.00%)	2/348 (0.57%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Joint-effusion ^† 1	0/337 (0.00%)	1/348 (0.29%)
Muscle weakness, not d/t neuropathy - Extrem-lower ^† 1	0/337 (0.00%)	1/348 (0.29%)
Muscle weakness, not d/t neuropathy - body/general ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pain - Back ^† 1	0/337 (0.00%)	3/348 (0.86%)
Pain - Bone ^† 1	1/337 (0.30%)	1/348 (0.29%)
Pain - Joint ^† 1	0/337 (0.00%)	2/348 (0.57%)
Pain - Muscle ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pain - Neck ^† 1	0/337 (0.00%)	2/348 (0.57%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS ^† 1	10/337 (2.97%)	4/348 (1.15%)
Nervous system disorders
CNS cerebrovascular ischemia ^† 1	0/337 (0.00%)	1/348 (0.29%)
Cognitive disturbance ^† 1	0/337 (0.00%)	1/348 (0.29%)
Dizziness ^† 1	0/337 (0.00%)	1/348 (0.29%)
Hemorrhage, CNS ^† 1	1/337 (0.30%)	0/348 (0.00%)
Neurology-Other ^† 1	0/337 (0.00%)	1/348 (0.29%)
Somnolence/depressed level of consciousness ^† 1	0/337 (0.00%)	2/348 (0.57%)
Speech impairment (e.g., dysphasia or aphasia) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Syncope (fainting) ^† 1	0/337 (0.00%)	1/348 (0.29%)
Psychiatric disorders
Confusion ^† 1	1/337 (0.30%)	1/348 (0.29%)
Mood alteration - agitation ^† 1	0/337 (0.00%)	1/348 (0.29%)
Renal and urinary disorders
Renal failure ^† 1	0/337 (0.00%)	1/348 (0.29%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS) ^† 1	1/337 (0.30%)	0/348 (0.00%)
Dyspnea (shortness of breath) ^† 1	5/337 (1.48%)	1/348 (0.29%)
Hypoxia ^† 1	2/337 (0.59%)	2/348 (0.57%)
Pain - Pleura ^† 1	0/337 (0.00%)	1/348 (0.29%)
Pneumonitis/pulmonary infiltrates ^† 1	0/337 (0.00%)	1/348 (0.29%)
Vascular disorders
Hypotension ^† 1	0/337 (0.00%)	2/348 (0.57%)
Thrombosis/thrombus/embolism ^† 1	1/337 (0.30%)	5/348 (1.44%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Anastrozole	Anastrozole & Fulvestrant
	Affected / at Risk (%)	Affected / at Risk (%)
Total	309/337 (91.69%)	322/348 (92.53%)
Blood and lymphatic system disorders
Hemoglobin ^† 1	64/337 (18.99%)	80/348 (22.99%)
Gastrointestinal disorders
Constipation ^† 1	89/337 (26.41%)	110/348 (31.61%)
Diarrhea ^† 1	64/337 (18.99%)	72/348 (20.69%)
Dry mouth/salivary gland (xerostomia) ^† 1	46/337 (13.65%)	47/348 (13.51%)
Heartburn/dyspepsia ^† 1	26/337 (7.72%)	15/348 (4.31%)
Nausea ^† 1	114/337 (33.83%)	119/348 (34.20%)
Pain - Abdomen NOS ^† 1	41/337 (12.17%)	47/348 (13.51%)
Vomiting ^† 1	60/337 (17.80%)	57/348 (16.38%)
General disorders
Edema: limb ^† 1	72/337 (21.36%)	89/348 (25.57%)
Fatigue (asthenia, lethargy, malaise) ^† 1	203/337 (60.24%)	220/348 (63.22%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L ^† 1	26/337 (7.72%)	21/348 (6.03%)
Injection site reaction/extravasation changes ^† 1	4/337 (1.19%)	48/348 (13.79%)
Pain - Chest/thorax NOS ^† 1	27/337 (8.01%)	52/348 (14.94%)
Pain-Other ^† 1	83/337 (24.63%)	108/348 (31.03%)
Rigors/chills ^† 1	28/337 (8.31%)	20/348 (5.75%)
Infections and infestations
Infection with unknown ANC - Urinary tract NOS ^† 1	18/337 (5.34%)	22/348 (6.32%)
Infection-Other ^† 1	40/337 (11.87%)	47/348 (13.51%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) ^† 1	36/337 (10.68%)	25/348 (7.18%)
AST, SGOT ^† 1	52/337 (15.43%)	43/348 (12.36%)
Alkaline phosphatase ^† 1	36/337 (10.68%)	46/348 (13.22%)
Creatinine ^† 1	36/337 (10.68%)	47/348 (13.51%)
Leukocytes (total WBC) ^† 1	37/337 (10.98%)	34/348 (9.77%)
Lymphopenia ^† 1	10/337 (2.97%)	22/348 (6.32%)
Platelets ^† 1	14/337 (4.15%)	26/348 (7.47%)
Weight gain ^† 1	31/337 (9.20%)	42/348 (12.07%)
Weight loss ^† 1	24/337 (7.12%)	21/348 (6.03%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) ^† 1	18/337 (5.34%)	18/348 (5.17%)
Anorexia ^† 1	78/337 (23.15%)	74/348 (21.26%)
Calcium, serum-high (hypercalcemia) ^† 1	20/337 (5.93%)	25/348 (7.18%)
Calcium, serum-low (hypocalcemia) ^† 1	20/337 (5.93%)	25/348 (7.18%)
Glucose, serum-high (hyperglycemia) ^† 1	73/337 (21.66%)	95/348 (27.30%)
Glucose, serum-low (hypoglycemia) ^† 1	6/337 (1.78%)	18/348 (5.17%)
Potassium, serum-high (hyperkalemia) ^† 1	11/337 (3.26%)	25/348 (7.18%)
Potassium, serum-low (hypokalemia) ^† 1	27/337 (8.01%)	31/348 (8.91%)
Sodium, serum-low (hyponatremia) ^† 1	26/337 (7.72%)	29/348 (8.33%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - body/general ^† 1	12/337 (3.56%)	18/348 (5.17%)
Pain - Back ^† 1	135/337 (40.06%)	130/348 (37.36%)
Pain - Bone ^† 1	93/337 (27.60%)	113/348 (32.47%)
Pain - Extremity-limb ^† 1	35/337 (10.39%)	47/348 (13.51%)
Pain - Joint ^† 1	152/337 (45.10%)	153/348 (43.97%)
Pain - Muscle ^† 1	80/337 (23.74%)	79/348 (22.70%)
Nervous system disorders
Dizziness ^† 1	59/337 (17.51%)	65/348 (18.68%)
Neuropathy: motor ^† 1	27/337 (8.01%)	21/348 (6.03%)
Neuropathy: sensory ^† 1	69/337 (20.47%)	92/348 (26.44%)
Pain - Head/headache ^† 1	66/337 (19.58%)	81/348 (23.28%)
Psychiatric disorders
Confusion ^† 1	19/337 (5.64%)	15/348 (4.31%)
Insomnia ^† 1	95/337 (28.19%)	97/348 (27.87%)
Mood alteration - agitation ^† 1	13/337 (3.86%)	18/348 (5.17%)
Mood alteration - anxiety ^† 1	58/337 (17.21%)	58/348 (16.67%)
Mood alteration - depression ^† 1	63/337 (18.69%)	79/348 (22.70%)
Renal and urinary disorders
Urinary frequency/urgency ^† 1	8/337 (2.37%)	20/348 (5.75%)
Reproductive system and breast disorders
Pain - Pelvis ^† 1	17/337 (5.04%)	24/348 (6.90%)
Vaginal dryness ^† 1	22/337 (6.53%)	24/348 (6.90%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	8/337 (2.37%)	19/348 (5.46%)
Cough ^† 1	91/337 (27.00%)	92/348 (26.44%)
Dyspnea (shortness of breath) ^† 1	96/337 (28.49%)	102/348 (29.31%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other ^† 1	12/337 (3.56%)	19/348 (5.46%)
Hair loss/Alopecia (scalp or body) ^† 1	11/337 (3.26%)	23/348 (6.61%)
Pruritus/itching ^† 1	27/337 (8.01%)	45/348 (12.93%)
Rash/desquamation ^† 1	45/337 (13.35%)	61/348 (17.53%)
Sweating (diaphoresis) ^† 1	53/337 (15.73%)	62/348 (17.82%)
Vascular disorders
Hot flashes/flushes ^† 1	154/337 (45.70%)	189/348 (54.31%)
Hypertension ^† 1	49/337 (14.54%)	53/348 (15.23%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

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Name/Title:	Breast Committee Statistician
Organization:	SWOG
Phone:	206-667-4623

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Linden HH, Livingston RB, Hortobagyi GN. Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer. N Engl J Med. 2019 Mar 28;380(13):1226-1234. doi: 10.1056/NEJMoa1811714. Erratum In: N Engl J Med. 2019 Jun 06;380(23):2282.

Unger JM, LeBlanc M, Blanke CD. The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population. JAMA Oncol. 2017 Oct 1;3(10):1345-1351. doi: 10.1001/jamaoncol.2017.0762.

Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. doi: 10.1056/NEJMoa1201622.

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Responsible Party:	SWOG Cancer Research Network
ClinicalTrials.gov Identifier:	NCT00075764
Other Study ID Numbers:	CDR0000349337 U10CA032102 ( U.S. NIH Grant/Contract ) S0226 ( Other Identifier: SWOG ) CAN-NCIC-MAC7 ( Other Identifier: NCIC-CTG )
First Submitted:	January 9, 2004
First Posted:	January 13, 2004
Results First Submitted:	October 26, 2016
Results First Posted:	April 4, 2017
Last Update Posted:	January 13, 2021

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