A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease

Overall survival (OS)

The OS is defined as the time from randomization to death due to any cause.

Time frame: From randomization until the date of death due to any cause (up to 8 years)

Second progression-free survival (PFS2)

Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.

Time frame: From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)

Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1

ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 1.1.

Time frame: From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (up to 5 years)

Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1

The DoR will be 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 the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)

Time to chemotherapy (TTC)

Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.

Time frame: From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)

Time to first subsequent anti-cancer therapy (TFST)

TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.

Time frame: From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years)

Clinical benefit rate at 24 weeks (CBR24)

CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window).

Time frame: At least 23 weeks after randomisation

Time to second subsequent therapy (TSST)

TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.

Time frame: From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years)

Plasma concentration of AZD9833 at specified timepoints

To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.

Time frame: on Day 15

Change from baseline in EORTC QLQ-C30 scale scores

Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Time frame: From baseline to 24 weeks post progression (up to approximately 5 years)

Change from baseline in EORTC QLQ-BR45 scale scores

Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Time frame: From baseline to 24 weeks post progression (up to approximately 5 years)