Trial Outcomes & Findings for A Clinical Trial to Compare Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg (NCT NCT00313170)

Last Updated: 2020-01-06

Results Overview

Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

144 participants

Primary outcome timeframe

The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Results posted on

2020-01-06

Participant Flow

Postmenopausal women with oestrogen receptor positive advanced breast cancer progressing or relapsing after previous endocrine therapy were randomised between 30th May 2006 and 30th November 2007

Participant milestones

Participant milestones
Measure	Fulvestrant 250 mg Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg Fulvestrant 500 mg
Overall Study STARTED	47	51	46
Overall Study COMPLETED	11	17	14
Overall Study NOT COMPLETED	36	34	32

Reasons for withdrawal

Reasons for withdrawal
Measure	Fulvestrant 250 mg Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg Fulvestrant 500 mg
Overall Study Death	2	4	2
Overall Study Adverse Event	1	2	0
Overall Study Disease progression	31	26	27
Overall Study Withdrawal by Subject	1	0	1
Overall Study Incorrect enrollment	0	2	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Progression (investigators opinion)	1	0	0

Baseline Characteristics

A Clinical Trial to Compare Efficacy and Tolerability of Fulvestrant 250mg, 250mg Plus 250mg Loading Regimen and 500mg

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fulvestrant 250 mg n=47 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=51 Participants Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 Participants Fulvestrant 500 mg	Total n=144 Participants Total of all reporting groups
Age, Continuous	63.7 years STANDARD_DEVIATION 9.9 • n=5 Participants	68.1 years STANDARD_DEVIATION 9.9 • n=7 Participants	65.5 years STANDARD_DEVIATION 9.0 • n=5 Participants	65.8 years STANDARD_DEVIATION 9.8 • n=4 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	51 Participants n=7 Participants	46 Participants n=5 Participants	144 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	45 Participants n=5 Participants	51 Participants n=7 Participants	46 Participants n=5 Participants	142 Participants n=4 Participants
Race/Ethnicity, Customized Oriental (Japanese)	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Oriental (Asian other than Chinese or Japanese)	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=47 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=51 Participants Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 Participants Fulvestrant 500 mg
Objective Response (ORR)	8.5 Percentage of patients Interval 2.4 to 20.4	5.9 Percentage of patients Interval 1.2 to 16.2	15.2 Percentage of patients Interval 6.3 to 28.9

SECONDARY outcome

Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Population: Full analysis set

Time from randomisation until objective disease progression or death (in the absence of objective progression) using the Kaplan-Meier method. RECIST tumor assessments were carried out every 12 weeks until progression.

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=47 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=51 Participants Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 Participants Fulvestrant 500 mg
Time to Progression (TTP)	88 Days Interval 79.0 to 260.0	172 Days Interval 80.0 to 339.0	169 Days Interval 82.0 to 477.0

SECONDARY outcome

Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Population: All objective responders

DoR was defined as the time from date of first documentation of the response (CR or PR) until the date of disease progression or death from any cause.

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=4 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=3 Participants Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=7 Participants Fulvestrant 500 mg
Duration of Response (DoR)	NA Days not estimable	NA Days Interval 66.0 to median and 75th percentile not estimable	539 Days Interval 539.0 to 539.0

SECONDARY outcome

Timeframe: The planned data cut-off for this study was when all patients, except withdrawals, had been followed up for at least 24 weeks. Patients received treatment up to approximately 2 years.

Population: Full analysis set

CBR was defined as the proportion of all randomised patients who had clinical benefit (response of CR, PR or SD\>=24 weeks.

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=47 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=51 Participants Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 Participants Fulvestrant 500 mg
Clinical Benefit Rate (CBR)	31.9 Percentage of patients Interval 19.1 to 47.1	47.1 Percentage of patients Interval 32.9 to 61.5	47.8 Percentage of patients Interval 32.9 to 63.1

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Participants who had PK samples only

A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean.

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=72 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg Fulvestrant 500 mg
Pharmacokinetic Parameter: Mean Population Clearance, a Measure of the Efficiency With Which Fulvestrant is Eliminated From the Body	31 litres per hour Standard Error 3.29	—	—

SECONDARY outcome

Timeframe: Baseline to 12 weeks

A 2-compartment model with a 1st order absorption and 1st order elimination process was fitted to the fulvestrant concentration-time data. Relative standard error is reported for the mean. The mean estimate of volume of distribution at steady state was reported as the sum of V1/F and V2/F in the clinical study report.

Outcome measures

Outcome measures
Measure	Fulvestrant 250 mg n=72 Participants Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg Fulvestrant 500 mg
Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes V1/F	20600 Liters Standard Error 3.67	—	—
Pharmacokinetic Parameter: Mean Volume of Distribution at Steady State, a Measure of the Apparent Volume in the Body Into Which Fulvestrant Distributes V2/F	35700 Liters Standard Error 27.8	—	—

Adverse Events

Fulvestrant 250 mg

Serious events: 4 serious events

Other events: 36 other events

Deaths: 2 deaths

Fulvestrant 250 mg + Loading Dose

Serious events: 9 serious events

Other events: 35 other events

Deaths: 4 deaths

Fulvestrant 500 mg

Serious events: 4 serious events

Other events: 31 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Gerard Lynch

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Fulvestrant 250 mg n=47 participants at risk Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=50 participants at risk Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 participants at risk Fulvestrant 500 mg
Eye disorders Macular Hole	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Blood and lymphatic system disorders Anaemia	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Cardiac disorders Myocardial Infarction	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Diverticulum Intestinal Haemorrhagic	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Melaena	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
General disorders Pain	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Infections and infestations Pneumonia	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Injury, poisoning and procedural complications Meniscus Lesion	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Nervous system disorders Amnesia	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Nervous system disorders Ischaemic Stroke	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Psychiatric disorders Depression	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Psychiatric disorders Mental Disorder	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Renal and urinary disorders Renal Colic	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.0% 2/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Inflammation	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.

Other adverse events
Measure	Fulvestrant 250 mg n=47 participants at risk Fulvestrant 250 mg	Fulvestrant 250 mg + Loading Dose n=50 participants at risk Fulvestrant 250 mg + Loading Dose	Fulvestrant 500 mg n=46 participants at risk Fulvestrant 500 mg
Gastrointestinal disorders Abdominal Pain Upper	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.3% 2/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Abdominal Pain	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Constipation	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	14.0% 7/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Diarrhoea	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	13.0% 6/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Nausea	25.5% 12/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	18.0% 9/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	15.2% 7/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Gastrointestinal disorders Vomiting	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	10.9% 5/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
General disorders Asthenia	10.6% 5/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.7% 4/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
General disorders Fatigue	8.5% 4/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	22.0% 11/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	15.2% 7/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
General disorders Oedema Peripheral	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.3% 2/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
General disorders Injection Site Pain	12.8% 6/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	14.0% 7/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	13.0% 6/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Infections and infestations Herpes Zoster	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Infections and infestations Nasopharyngitis	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Infections and infestations Urinary Tract Infection	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Investigations Weight Decreased	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	12.0% 6/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Metabolism and nutrition disorders Anorexia	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Arthralgia	8.5% 4/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	14.0% 7/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.7% 4/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Back Pain	10.6% 5/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	16.0% 8/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	15.2% 7/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	8.5% 4/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.0% 2/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.3% 2/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Myalgia	12.8% 6/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.3% 2/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Musculoskeletal and connective tissue disorders Pain In Extremity	10.6% 5/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	10.0% 5/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Nervous system disorders Dizziness	2.1% 1/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Nervous system disorders Headache	10.6% 5/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Psychiatric disorders Anxiety	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	10.0% 5/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	4.3% 2/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Psychiatric disorders Depression	6.4% 3/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.0% 4/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Renal and urinary disorders Urinary Incontinence	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Cough	12.8% 6/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	12.0% 6/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	8.7% 4/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.8% 6/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	12.0% 6/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	10.9% 5/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Skin and subcutaneous tissue disorders Alopecia	4.3% 2/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.0% 1/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Vascular disorders Hot Flush	19.1% 9/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	10.0% 5/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.5% 3/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	0.00% 0/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.
Blood and lymphatic system disorders Anaemia	0.00% 0/47 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	6.0% 3/50 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.	2.2% 1/46 1 patient in the 250mg + LD arm was randomised but did not receive any randomised therapy. This patient is included in the efficacy summaries but is excluded from the safety summaries. All-Cause Mortality: patients who died whilst on study treatment or during 56 days after the last fulvestrant injection. Serious Adverse Events: Patients with SAE other than death are reported. NOTE: Other Adverse Events include serious and non-serious AEs.