Trial Outcomes & Findings for Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women (NCT NCT01300351)

Last Updated: 2015-04-24

Results Overview

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions, or death (by any cause in the absence of progression). The primary analysis for PFS was the log rank test stratified by last endocrine therapy received prior to fulvestrant (AO vs. AI). The treatment effect was estimated using the HR of 500 mg fulvestrant to 250 mg fulvestrant together with the corresponding 95% CI and p value.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

249 participants

Primary outcome timeframe

36 months

Results posted on

2015-04-24

Participant Flow

The planned population size was 220 randomised patients. 249 patients were enrolled with 28 screen-failured patients and altogether 221 patients were randomised. The recuitment period of this study took 34 months, first subject in on 01 Mar 2011 and last subject in on 23 Dec 2013.

The Enrollment number in the protocol section means the number of patients enter the trial and receiving screening procedure, the number of participants Started in the Participant Flow module means the number of randomized patients and do not include screening failure patients.

Participant milestones

Participant milestones
Measure	Fulvestrant 500 mg Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg Fulvestrant 250 mg im every 28 (± 3) days
Overall Study STARTED	111	110
Overall Study Received Study Treatment	109	110
Overall Study COMPLETED	75	72
Overall Study NOT COMPLETED	36	38

Reasons for withdrawal

Reasons for withdrawal
Measure	Fulvestrant 500 mg Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg Fulvestrant 250 mg im every 28 (± 3) days
Overall Study Did not receive treatment	2	0
Overall Study Ongoing treatment at data cut-off	27	23
Overall Study Lost to Follow-up	0	1
Overall Study Adverse Event	0	4
Overall Study Withdrawal by Subject	7	10

Baseline Characteristics

Comparing the Efficacy and Tolerability of Fulvestrant 500 mg Versus 250 mg in Advanced Breast Cancer Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fulvestrant 500 mg n=111 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=110 Participants Fulvestrant 250 mg im every 28 (± 3) days	Total n=221 Participants Total of all reporting groups
Age, Continuous	53.6 years STANDARD_DEVIATION 10.12 • n=5 Participants	53.1 years STANDARD_DEVIATION 10.22 • n=7 Participants	53.3 years STANDARD_DEVIATION 10.15 • n=5 Participants
Age, Customized <50 Years	37 participants n=5 Participants	40 participants n=7 Participants	77 participants n=5 Participants
Age, Customized ≥50 to <65 Years	61 participants n=5 Participants	56 participants n=7 Participants	117 participants n=5 Participants
Age, Customized ≥65 Years	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	110 Participants n=7 Participants	221 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	111 Participants n=5 Participants	110 Participants n=7 Participants	221 Participants n=5 Participants
Weight	61.0 kg n=5 Participants	60.5 kg n=7 Participants	60.7 kg n=5 Participants
WHO Performance Status (0) Normal activity	80 participants n=5 Participants	77 participants n=7 Participants	157 participants n=5 Participants
WHO Performance Status (1) Restricted activity	28 participants n=5 Participants	30 participants n=7 Participants	58 participants n=5 Participants
WHO Performance Status (2) In bed ≤50% of the time	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Extent of disease at baseline Locally advanced breast cancer only	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Extent of disease at baseline Metastatic disease	110 participants n=5 Participants	109 participants n=7 Participants	219 participants n=5 Participants

PRIMARY outcome

Timeframe: 36 months

Population: FAS: all randomised patients and compared the treatment groups on the basis of randomised treatment, regardless of treatment actually received.

Outcome measures

Outcome measures
Measure	Fulvestrant 500 mg n=111 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=110 Participants Fulvestrant 250 mg im every 28 (± 3) days
Progression-free Survival	8.0 months Interval 2.8 to 16.6	4.0 months Interval 2.7 to 11.1

SECONDARY outcome

Timeframe: 36 months

Population: Evaluable for Response Set, included all patients in the FAS with measurable disease at baseline.

The ORR is defined as the proportion of all randomized patients with measurable disease at baseline who have a best objective tumour response of either CR or PR per RECIST v1.1.

Outcome measures

Outcome measures
Measure	Fulvestrant 500 mg n=57 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=66 Participants Fulvestrant 250 mg im every 28 (± 3) days
Objective Response Rate	16 patients Interval 5.36 to 11.04	11 patients Interval 2.92 to 5.72

SECONDARY outcome

Timeframe: 36 months

Population: FAS

A clinical benefit (CB) responder is defined as a patient having a best overall response of either CR, PR or SD for at least 24 weeks per RECIST v1.1. As tumour assessments can occur ± 2 weeks of the specified time point, the CBR is defined as the proportion of patients in the FAS who have CB ≥ 22 weeks (or 154 days).

Outcome measures

Outcome measures
Measure	Fulvestrant 500 mg n=111 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=110 Participants Fulvestrant 250 mg im every 28 (± 3) days
Clinical Benefit Rate	53 patients	36 patients

SECONDARY outcome

Timeframe: 36 months

Population: Evaluable for Response Set

Duration of response (DoR) will be evaluated only for patients who have an objective response, and is defined as the time from the date of first documentation of objective response (i.e., the initial visit at which CR or PR was recorded) until the date of disease progression or death due to any cause (whichever is earlier). The time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR. Any patient who has not progressed or died by the date of DCO, or who has been lost to follow up, will be right-censored at the date of their last disease assessment.

Outcome measures

Outcome measures
Measure	Fulvestrant 500 mg n=16 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=11 Participants Fulvestrant 250 mg im every 28 (± 3) days
Duration of Response	16.6 months Interval 5.6 to The data is not available due to high percent (7/16, 43.75%) of patients censored.	22.2 months Interval 10.8 to The data is not available due to high percent (8/11, 72.73%) of patients censored.

SECONDARY outcome

Timeframe: 36 months

Population: FAS

Duration of clinical benefit (DoCB) will be evaluated only for patients who have CB, and is defined as the time from the date of randomisation until the date of disease progression or death from any cause, whichever is earlier. Any patient who has not progressed or died by the date of DCO or who has been lost to follow up will be right censored at the date of their last evaluable disease assessment.

Outcome measures

Outcome measures
Measure	Fulvestrant 500 mg n=53 Participants Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=36 Participants Fulvestrant 250 mg im every 28 (± 3) days
Duration of Clinical Benefit	14.3 months Interval 11.0 to 25.0	13.8 months Interval 11.0 to The data is not available due to high percent (21/36, 58.33%) of patients censored.

Adverse Events

Fulvestrant 500 mg

Serious events: 4 serious events

Other events: 68 other events

Deaths: 0 deaths

Fulvestrant 250 mg

Serious events: 9 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Guofei Dai

AstraZeneca China

Phone: +86 21 60301242

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Fulvestrant 500 mg n=109 participants at risk Fulvestrant 500 mg intramuscular (im) every 28 (± 3) days plus an additional 500 mg on Day 15 (± 3) of first month only	Fulvestrant 250 mg n=110 participants at risk Fulvestrant 250 mg im every 28 (± 3) days
Blood and lymphatic system disorders Anaemia	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.91% 1/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Blood and lymphatic system disorders Leukopenia	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Cardiac disorders Cardiac failure	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.91% 1/110 • Number of events 1 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
General disorders Pyrexia	0.92% 1/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	1.8% 2/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Hepatobiliary disorders Hepatic function abnormal	0.92% 1/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Infections and infestations Arthritis bacterial	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	1.8% 2/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Infections and infestations Lung infection	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Investigations Haemoglobin decreased	0.92% 1/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.91% 1/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Investigations Neutrophil count decreased	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Investigations Platelet count decreased	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.91% 1/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Musculoskeletal and connective tissue disorders Bone pain	0.92% 1/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Nervous system disorders Cerebral infarction	0.92% 1/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.00% 0/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/109 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.	0.91% 1/110 • Adverse Events will be collected from time of signature of informed consent throughout the treatment period and up to 8 weeks after the last injection of study medication.