Trial Outcomes & Findings for Anastrozole Monotherapy Versus Maximal Oestrogen Blockade With Anastrozole and Fulvestrant Combination Therapy (NCT NCT00256698)
NCT ID: NCT00256698
Last Updated: 2012-08-01
Results Overview
RECIST (Response Evaluation Criteria in Solid Tumours) assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009. TTP, time in months to worsen 'progression' according to RECIST criteria. (RECIST is a set of published rules that define when cancer patients improve "respond", stay the same "stable"or worsen "progression" during treatments.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
514 participants
Primary outcome timeframe
RECIST assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009
Results posted on
2012-08-01
Participant Flow
258 patients were randomised to Fulvestrant + Anastrozole and 256 patients were randomised to Anastrozole. In each treatment group, there were 2 patients who did not receive any trial therapy and so have been excluded from the safety summaries.
Participant milestones
| Measure |
Fulvestrant + Anastrozole
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
Anastrozole 1 mg
|
|---|---|---|
|
Overall Study
STARTED
|
258
|
256
|
|
Overall Study
COMPLETED
|
91
|
84
|
|
Overall Study
NOT COMPLETED
|
167
|
172
|
Reasons for withdrawal
| Measure |
Fulvestrant + Anastrozole
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
Anastrozole 1 mg
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
7
|
|
Overall Study
Adverse Event
|
13
|
6
|
|
Overall Study
Protocol Violation
|
6
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
disease progression
|
97
|
105
|
|
Overall Study
still ongoing at data cut-off
|
41
|
46
|
|
Overall Study
withdrawn due to osteoporosis
|
1
|
0
|
|
Overall Study
Prematurely Discontinued
|
1
|
0
|
Baseline Characteristics
Anastrozole Monotherapy Versus Maximal Oestrogen Blockade With Anastrozole and Fulvestrant Combination Therapy
Baseline characteristics by cohort
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
Total
n=514 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
65.2 Years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
63.4 Years
STANDARD_DEVIATION 10.3 • n=7 Participants
|
64.3 Years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
258 Participants
n=5 Participants
|
256 Participants
n=7 Participants
|
514 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: RECIST assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009RECIST (Response Evaluation Criteria in Solid Tumours) assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009. TTP, time in months to worsen 'progression' according to RECIST criteria. (RECIST is a set of published rules that define when cancer patients improve "respond", stay the same "stable"or worsen "progression" during treatments.
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Time to Progression (TTP)
|
10.8 months
Interval 0.0 to 49.31
|
10.2 months
Interval 0.0 to 54.34
|
SECONDARY outcome
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009No. of patients who were objective responders over the no. of patients evaluable for response x100. An objective responder = a patient whose best response is either CR (disappearance of all lesions) or PR (\>= 30% shrinkage in the sum of the longest diamemeters of the measurable lesions + no new lesions + no progression of non-measurable lesions)
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=129 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=113 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Percentage of Evaluable Participants With Objective Response Rate (ORR)
|
31.8 Percentage of evaluable participants
|
33.6 Percentage of evaluable participants
|
SECONDARY outcome
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009No. of patients who were clinical benefit responders over the no. of randomised patients x100. A clinical benefit responder = a patient whose best response is CR, PR or SD\>=24 weeks (where a best response of SD = no new lesions and for existing lesions; neither suffient shrinkage to count as PR nor sufficient growth to count as progression)
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Percentage of Clinical Benefit Rate (CBR) Responders
|
55.0 Percentage of participants
|
55.1 Percentage of participants
|
SECONDARY outcome
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are objective responders
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=129 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=113 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Duration of Response (DoR)
|
22.3 months
Interval 5.55 to 46.95
|
18.2 months
Interval 7.2 to 49.77
|
SECONDARY outcome
Timeframe: RECIST tumour assessments carried out every 8 weeks from randomisation until data cut-off on 30th April 2009Median time from randomisation until objective progression or death (in the absence of objective progression), measured only in those patients who are clinical benefit responders
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Duration of Clinical Benefit (DoCB)
|
18.5 months
Interval 1.64 to 46.95
|
18.1 months
Interval 5.19 to 54.34
|
SECONDARY outcome
Timeframe: From randomisation until data cut-off on 30th April 2009Time from randomisation until the date of discontinuation of randomised treatment for any reason
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Time to Treatment Failure (TTF)
|
12.4 months
Interval 0.0 to 46.95
|
11.4 months
Interval 0.0 to 54.34
|
SECONDARY outcome
Timeframe: All deaths occurring between randomisation and data cut-off on 30th April 2009 are included.Overall survival is equivalent to time to death. Time from randomisation until the date of death
Outcome measures
| Measure |
Fulvestrant + Anastrozole
n=258 Participants
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=256 Participants
Anastrozole 1 mg
|
|---|---|---|
|
Overall Survival (OS)
|
37.8 months
Interval 0.07 to 61.86
|
38.2 months
Interval 0.13 to 60.39
|
Adverse Events
Fulvestrant + Anastrozole
Serious events: 40 serious events
Other events: 161 other events
Deaths: 0 deaths
Anastrozole
Serious events: 45 serious events
Other events: 178 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fulvestrant + Anastrozole
n=256 participants at risk
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=254 participants at risk
Anastrozole 1 mg
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.39%
1/256
|
0.39%
1/254
|
|
Cardiac disorders
Cardiac Failure
|
1.2%
3/256
|
0.39%
1/254
|
|
Cardiac disorders
Pericardial Effusion
|
0.00%
0/256
|
0.79%
2/254
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/256
|
0.39%
1/254
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/256
|
0.39%
1/254
|
|
Cardiac disorders
Atrial Flutter
|
0.00%
0/256
|
0.39%
1/254
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/256
|
0.39%
1/254
|
|
Cardiac disorders
Atrial Fibrillation
|
0.39%
1/256
|
0.00%
0/254
|
|
Cardiac disorders
Bradycardia
|
0.39%
1/256
|
0.00%
0/254
|
|
Cardiac disorders
Cardiomyopathy
|
0.39%
1/256
|
0.00%
0/254
|
|
Cardiac disorders
Myocardial Infarction
|
0.39%
1/256
|
0.00%
0/254
|
|
Cardiac disorders
Ventricular Arrhythmia
|
0.39%
1/256
|
0.00%
0/254
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/256
|
0.79%
2/254
|
|
Gastrointestinal disorders
Nausea
|
0.78%
2/256
|
0.79%
2/254
|
|
Gastrointestinal disorders
Diarrhoea
|
0.78%
2/256
|
0.00%
0/254
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/256
|
0.39%
1/254
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.39%
1/256
|
0.00%
0/254
|
|
Gastrointestinal disorders
Ileus
|
0.39%
1/256
|
0.00%
0/254
|
|
Gastrointestinal disorders
Pancreatitis
|
0.39%
1/256
|
0.00%
0/254
|
|
Gastrointestinal disorders
Vomiting
|
0.39%
1/256
|
0.00%
0/254
|
|
General disorders
General Physical Health Deterioration
|
0.00%
0/256
|
1.2%
3/254
|
|
General disorders
Chest Pain
|
0.39%
1/256
|
0.79%
2/254
|
|
General disorders
Pain
|
0.00%
0/256
|
0.79%
2/254
|
|
General disorders
Fatigue
|
0.78%
2/256
|
0.39%
1/254
|
|
General disorders
Oedema Peripheral
|
0.39%
1/256
|
0.00%
0/254
|
|
General disorders
Pyrexia
|
0.39%
1/256
|
0.00%
0/254
|
|
Infections and infestations
Pneumonia
|
1.2%
3/256
|
0.79%
2/254
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/256
|
0.79%
2/254
|
|
Infections and infestations
Infection
|
0.78%
2/256
|
0.00%
0/254
|
|
Infections and infestations
Sepsis
|
0.78%
2/256
|
0.00%
0/254
|
|
Infections and infestations
Bronchitis
|
0.00%
0/256
|
0.39%
1/254
|
|
Infections and infestations
Gangrene
|
0.00%
0/256
|
0.39%
1/254
|
|
Infections and infestations
Viral Infection
|
0.00%
0/256
|
0.39%
1/254
|
|
Infections and infestations
Bronchpneumonia
|
0.39%
1/256
|
0.00%
0/254
|
|
Infections and infestations
Erysipelas
|
0.39%
1/256
|
0.00%
0/254
|
|
Infections and infestations
Gastroenteritis
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
0.00%
0/256
|
0.79%
2/254
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
0.78%
2/256
|
0.39%
1/254
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.00%
0/256
|
0.39%
1/254
|
|
Injury, poisoning and procedural complications
Pelvic Fracture
|
0.00%
0/256
|
0.39%
1/254
|
|
Injury, poisoning and procedural complications
Fall
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Femoral Neck Fracture
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Fractured Sacrum
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Head Injury
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Joint Dislocation
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
0.39%
1/256
|
0.00%
0/254
|
|
Injury, poisoning and procedural complications
Blood Creatinine Increased
|
0.00%
0/256
|
0.39%
1/254
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/256
|
0.79%
2/254
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/256
|
0.39%
1/254
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/256
|
0.39%
1/254
|
|
Metabolism and nutrition disorders
Dehydration
|
0.39%
1/256
|
0.00%
0/254
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/256
|
0.79%
2/254
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.78%
2/256
|
0.00%
0/254
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/256
|
0.39%
1/254
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/256
|
0.39%
1/254
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/256
|
0.39%
1/254
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/256
|
0.39%
1/254
|
|
Musculoskeletal and connective tissue disorders
Spinal Column Stenosis
|
0.00%
0/256
|
0.39%
1/254
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.39%
1/256
|
0.00%
0/254
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.39%
1/256
|
0.00%
0/254
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
0.00%
0/256
|
0.39%
1/254
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.00%
0/256
|
0.39%
1/254
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Meninges
|
0.00%
0/256
|
0.39%
1/254
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer
|
0.00%
0/256
|
0.39%
1/254
|
|
Nervous system disorders
Dizziness
|
0.78%
2/256
|
0.79%
2/254
|
|
Nervous system disorders
Syncope
|
0.78%
2/256
|
0.39%
1/254
|
|
Nervous system disorders
Headache
|
0.39%
1/256
|
0.39%
1/254
|
|
Nervous system disorders
Intracranial Haematoma
|
0.00%
0/256
|
0.39%
1/254
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
0.00%
0/256
|
0.39%
1/254
|
|
Nervous system disorders
Cerebellar Infarction
|
0.39%
1/256
|
0.00%
0/254
|
|
Nervous system disorders
Cerebral Infarction
|
0.39%
1/256
|
0.00%
0/254
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
0.39%
1/256
|
0.00%
0/254
|
|
Nervous system disorders
Spinal Cord Compression
|
0.39%
1/256
|
0.00%
0/254
|
|
Nervous system disorders
Syncope Vasovagal
|
0.39%
1/256
|
0.00%
0/254
|
|
Psychiatric disorders
Depression
|
0.00%
0/256
|
0.39%
1/254
|
|
Psychiatric disorders
Schizophrenia
|
0.00%
0/256
|
0.39%
1/254
|
|
Psychiatric disorders
Confusional State
|
0.39%
1/256
|
0.00%
0/254
|
|
Renal and urinary disorders
Renal Failure
|
0.78%
2/256
|
0.00%
0/254
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
3/256
|
0.79%
2/254
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.2%
3/256
|
0.00%
0/254
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.78%
2/256
|
0.00%
0/254
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain
|
0.00%
0/256
|
0.39%
1/254
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/256
|
0.39%
1/254
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.39%
1/256
|
0.39%
1/254
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.39%
1/256
|
0.00%
0/254
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.39%
1/256
|
0.00%
0/254
|
|
General disorders
Foot Amputation
|
0.00%
0/256
|
0.39%
1/254
|
|
Vascular disorders
Venous Stasis
|
0.00%
0/256
|
0.39%
1/254
|
|
Vascular disorders
Thrombosis
|
0.39%
1/256
|
0.00%
0/254
|
Other adverse events
| Measure |
Fulvestrant + Anastrozole
n=256 participants at risk
Fulvestrant 250 mg Loading Dose Regimen + Anastrozole 1 mg
|
Anastrozole
n=254 participants at risk
Anastrozole 1 mg
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
9.0%
23/256
|
10.6%
27/254
|
|
Gastrointestinal disorders
Constipation
|
5.9%
15/256
|
4.7%
12/254
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
15/256
|
5.1%
13/254
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
13/256
|
3.5%
9/254
|
|
General disorders
Fatigue
|
10.5%
27/256
|
13.0%
33/254
|
|
Infections and infestations
Urinary tract infection
|
5.5%
14/256
|
3.1%
8/254
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.7%
30/256
|
10.6%
27/254
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.1%
8/256
|
7.9%
20/254
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.3%
11/256
|
5.9%
15/254
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.9%
10/256
|
5.1%
13/254
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.1%
13/256
|
3.5%
9/254
|
|
Vascular disorders
Hot flush
|
8.2%
21/256
|
7.5%
19/254
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that they cannot disclose or publish any information to do with the trial without consent from AstraZeneca
- Publication restrictions are in place
Restriction type: OTHER