A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer

PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Time frame: From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)

Population: FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.

Time frame: From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)

Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization. Adjusted response rate was presented in this analysis. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Time frame: At Week 24

Population: FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.

Time frame: From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)

ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Adjusted response rate was presented in this analysis. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Time frame: From screening until disease progression (up to data cut-off of 29 months)

Population: A subset of the FAS with measurable disease.

The OS was defined as the time from randomisation to death due to any cause.

Time frame: From the date of randomisation until death (up to data cut-off of 29 months)

The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.

Time frame: At Week 16

The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.

Time frame: From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)

The plasma concentrations of AZD9833 at steady state were evaluated.

Time frame: Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)

Population: The PK Analysis Set consisted of all patients who received at least one dose of AZD9833 per protocol, for whom there is at least one reportable PK concentration.

The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated.

Time frame: From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)

Population: Safety analysis set consisted of all patients who received any amount of study treatment (AZD9833 or fulvestrant), regardless of whether that was the randomised therapy intended or whether they received therapy without being randomised and for whom any post-dose data are available.