Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer) (NCT NCT04576455)

NCT ID: NCT04576455

Last Updated: 2026-01-16

Results Overview

PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). 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. Kaplan-Meier methodology was used to estimate median PFS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 303 participants
• Primary outcome timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months)
• Results posted on: 2026-01-16

Participant Flow

Participants were enrolled in this study at 85 investigational sites in the following countries: Argentina, Australia, Brazil, China, Germany, Israel, Poland, Republic of Korea, Russian Federation, Singapore, South Africa, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, and the United States. The study is ongoing.

A total of 303 participants were enrolled in this study, one of whom was randomized to the giredestrant arm and received fulvestrant in error and was grouped in the physician's choice of endocrine monotherapy (PCET) arm for safety analysis.

Participant milestones

Measure	Physician's Choice of Endocrine Monotherapy Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.	Giredestrant Participants received giredestrant, 30 milligrams (mg), orally (PO), once daily (QD), on Days 1-28 (and luteinizing hormone-releasing hormone \[LHRH\] agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.
Overall Study STARTED	152	151
Overall Study Safety-Evaluable Population	152	150
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	152	151

Reasons for withdrawal

Measure	Physician's Choice of Endocrine Monotherapy Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.	Giredestrant Participants received giredestrant, 30 milligrams (mg), orally (PO), once daily (QD), on Days 1-28 (and luteinizing hormone-releasing hormone \[LHRH\] agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.
Overall Study Ongoing in the Study	58	48
Overall Study Death	77	83
Overall Study Lost to Follow-up	5	4
Overall Study Withdrawal by Subject	12	16

Baseline Characteristics

A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)

Baseline characteristics by cohort

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.	Total n=303 Participants Total of all reporting groups
Age, Continuous	59.5 years STANDARD_DEVIATION 12.4 • n=9 Participants	57.8 years STANDARD_DEVIATION 10.7 • n=6 Participants	58.6 years STANDARD_DEVIATION 11.6 • n=9 Participants
Sex: Female, Male Female	151 Participants n=9 Participants	151 Participants n=6 Participants	302 Participants n=9 Participants
Sex: Female, Male Male	0 Participants n=9 Participants	1 Participants n=6 Participants	1 Participants n=9 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	23 Participants n=9 Participants	20 Participants n=6 Participants	43 Participants n=9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	128 Participants n=9 Participants	132 Participants n=6 Participants	260 Participants n=9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=9 Participants	0 Participants n=6 Participants	1 Participants n=9 Participants
Race (NIH/OMB) Asian	58 Participants n=9 Participants	66 Participants n=6 Participants	124 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=6 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	2 Participants n=9 Participants	2 Participants n=6 Participants	4 Participants n=9 Participants
Race (NIH/OMB) White	89 Participants n=9 Participants	81 Participants n=6 Participants	170 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	1 Participants n=6 Participants	1 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=9 Participants	2 Participants n=6 Participants	3 Participants n=9 Participants
Site of Disease (Visceral or Non-Visceral) Visceral Disease	109 Participants n=9 Participants	110 Participants n=6 Participants	219 Participants n=9 Participants
Site of Disease (Visceral or Non-Visceral) Non-visceral Disease	42 Participants n=9 Participants	42 Participants n=6 Participants	84 Participants n=9 Participants
Prior Treatment With CDK4/6 Inhibitor (Yes or No) Yes, Prior Treatment With CDK4/6 Inhibitor	63 Participants n=9 Participants	62 Participants n=6 Participants	125 Participants n=9 Participants
Prior Treatment With CDK4/6 Inhibitor (Yes or No) No Prior Treatment With CDK4/6 Inhibitor	88 Participants n=9 Participants	90 Participants n=6 Participants	178 Participants n=9 Participants
Prior Treatment With Fulvestrant (Yes or No) Yes, Prior Treatment With Fulvestrant	29 Participants n=9 Participants	29 Participants n=6 Participants	58 Participants n=9 Participants
Prior Treatment With Fulvestrant (Yes or No) No Prior Treatment With Fulvestrant	122 Participants n=9 Participants	123 Participants n=6 Participants	245 Participants n=9 Participants
Estrogen Receptor (ESR1) Mutation Status ESR1 mutation detected	51 Participants n=9 Participants	39 Participants n=6 Participants	90 Participants n=9 Participants
Estrogen Receptor (ESR1) Mutation Status ESR1 no mutation detected	66 Participants n=9 Participants	76 Participants n=6 Participants	142 Participants n=9 Participants
Estrogen Receptor (ESR1) Mutation Status Not Evaluable	34 Participants n=9 Participants	37 Participants n=6 Participants	71 Participants n=9 Participants

PRIMARY outcome

Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). 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. Kaplan-Meier methodology was used to estimate median PFS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	5.55 months Interval 4.93 to 7.36	5.36 months Interval 3.71 to 5.55

SECONDARY outcome

Timeframe: From randomization to death from any cause (duration of follow-up, median [range]: 34.6 [0.0-41.8] months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

Overall survival (OS) is defined as the Kaplan-Meier estimate of time from randomization to death from any cause. Kaplan-Meier methodology was used to estimate median OS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Analysis strata are: Site of disease, Prior treatment with CDK4/6 inhibitor and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression. Data for participants who were alive at the time of the analysis data cutoff were censored at the last date they were known to be alive. Data from participants without postbaseline information were censored at the date of randomization plus 1 day.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Overall Survival (OS)	27.50 Months Interval 23.2 to 32.69	29.77 Months Interval 26.78 to The upper limit of the 95% confidence interval (CI) was not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From randomization until disease progression or death (up to approximately 15 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Objective Response Rate, as Determined by the Investigator According to RECIST v1.1	12.6 Percentage of participants Interval 7.75 to 18.95	7.2 Percentage of participants Interval 3.67 to 12.58

SECONDARY outcome

Timeframe: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 15 months)

DOR is defined as the Kaplan-Meier estimate of time from the first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Objective response rate is defined as the percentage of participants with a CR or PR on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

Outcome measures

Measure	Giredestrant n=19 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=11 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1	NA Months Interval 5.55 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.	7.39 Months Interval 7.39 to The upper limit of the 95% CI was not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From randomization until disease progression or death (up to approximately 15 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a CR or PR. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1	31.8 Percentage of participants Interval 24.46 to 39.85	21.1 Percentage of participants Interval 14.87 to 28.4

SECONDARY outcome

Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months)

Population: ctDNA-evaluable population included all FAS participants with evaluable plasma ctDNA at baseline. Number analyzed is the number of participants with data available for analysis at the specified time point. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Investigator-assessed PFS was analyzed in subgroups categorized by baseline ESR1 mutation status (i.e., with or without ESR1 mutation at baseline) from plasma circulating tumor deoxyribonucleic acid (ctDNA). Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.

Outcome measures

Measure	Giredestrant n=117 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=115 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor (ESR1) Mutation Status PFS by ESR1 Mutation Detected at Baseline	5.32 months Interval 3.61 to 5.59	3.48 months Interval 1.81 to 3.81
Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor (ESR1) Mutation Status PFS by ESR1 Mutation Not Detected at Baseline	7.20 months Interval 5.36 to 11.17	6.60 months Interval 5.32 to The upper limit of the 95% CI was not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From Baseline until treatment discontinuation (up to approximately 41 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

TTD in pain severity is defined as time to first documented ≥2-point increase from Baseline in the "Worst Pain" item from the BPI-SF Questionnaire held for at least two consecutive cycles or an initial ≥2-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 10-point numeric rating scale, with 0="No pain", "No interference" to 10="Pain as bad as you can imagine", "Highest imaginable interference". A lower score indicates improvement. 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Time to Deterioration (TTD) in Pain Severity, Based on the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire	28.65 months Interval 18.43 to The upper limit of the 95% CI was not evaluable because of an insufficient number of participants with the event.	NA months Interval 16.59 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From Baseline until treatment discontinuation (up to approximately 41 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

TTD in pain presence and interference is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed pain scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The pain scale is scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate worse pain symptoms. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
TTD in Pain Presence and Interference, Based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Pain Scale Score	22.14 months Interval 18.43 to The upper limit of the 95% CI was not evaluable because of an insufficient number of participants with the event.	NA months Interval 20.27 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From Baseline until treatment discontinuation (up to approximately 41 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

TTD in PF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The PF scale has 5 questions scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate better function. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
TTD in Physical Functioning (PF), Based on the EORTC QLQ-C30 PF Scale Score	NA months Interval 28.65 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.	NA months Interval 23.29 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From Baseline until treatment discontinuation (up to approximately 41 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

TTD in RF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The RF is scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate better function. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
TTD in Role Functioning (RF), Based on the EORTC QLQ-C30 RF Scale Score	NA months Interval 18.43 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.	NA months Interval 22.31 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From Baseline until treatment discontinuation (up to approximately 41 months)

Population: FAS included all participants assigned to treatment groups as randomized by the IxRS.

TTD in GHS/QoL is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent); higher scores indicate better QoL. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.

Outcome measures

Measure	Giredestrant n=151 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 Participants Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
TTD in Global Health Status and Quality of Life (GHS/QoL), Based on the EORTC QLQ-C30 GHS/QoL Scale Score	NA months Interval 31.38 to The median and the upper limit of the 95% CI were not evaluable because of an insufficient number of participants with the event.	NA months The median and the 95% CI were not evaluable because of an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: From first dose until 30 days after final dose of study drug (up to approximately 55 months)

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition; any deterioration in a laboratory value or other clinical test; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 55 months)

Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 55 months)

Hematology parameters include white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to approximately 55 months)

Biochemistry parameters include bicarbonate or total carbon dioxide, sodium, potassium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, calcium, total and direct bilirubin, alkaline phosphatase level test (ALP), Alanine transaminase (ALT), aspartate aminotransferase (AST), urate, and lactate dehydrogenase (LDH).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 1 3-hours postdose, Cycle 2 Day 1 predose, Cycle 2 Day 1 3-hour postdose, Cycle 3 Day 1 predose

Population: Pharmacokinetics (PK)-Evaluable Population: All randomized patients in the giredestrant arm who had at least one evaluable post-dose giredestrant plasma concentration. The overall number of participants analyzed is the total number of unique participants who had an evaluable PK sample for at least one timepoint. The number analyzed at a given timepoint indicates those with an evaluable sample for the specified timepoint.

Outcome measures

Measure	Giredestrant n=148 Participants Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Plasma Concentration of Giredestrant at Specified Timepoints Cycle 1 Day 1 3-hours postdose	117 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 107	—
Plasma Concentration of Giredestrant at Specified Timepoints Cycle 2 Day 1 predose	171 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 64.5	—
Plasma Concentration of Giredestrant at Specified Timepoints Cycle 2 Day 1 3-hour postdose	268 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 57.6	—
Plasma Concentration of Giredestrant at Specified Timepoints Cycle 3 Day 1 predose	151 nanograms per millilitre (ng/mL) Geometric Coefficient of Variation 68.5	—

Adverse Events

Giredestrant

Serious events: 20 serious events

Other events: 108 other events

Deaths: 83 deaths

Physician's Choice of Endocrine Monotherapy

Serious events: 15 serious events

Other events: 87 other events

Deaths: 77 deaths

Serious adverse events

Measure	Giredestrant n=150 participants at risk Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 participants at risk Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Blood and lymphatic system disorders Anaemia	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Cardiac disorders Cardiac failure	1.3% 2/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Cardiac disorders Cardiac failure acute	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Cardiac disorders Myocardial infarction	1.3% 2/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Cardiac disorders Pericardial effusion	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Diarrhoea	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Vomiting	1.3% 2/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
General disorders Asthenia	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations Arthritis bacterial	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations COVID-19	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	1.3% 2/152 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations COVID-19 pneumonia	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations Viral infection	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Femur fracture	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Vascular graft stenosis	0.67% 1/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Alanine aminotransferase increased	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Aspartate aminotransferase increased	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Blood bilirubin increased	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Arthralgia	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Bone pain	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Cerebral infarction	1.3% 2/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Epilepsy	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Ischaemic stroke	1.3% 2/150 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Partial seizures	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Renal and urinary disorders Renal failure	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations Pneumonia	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations Streptococcal sepsis	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Metabolism and nutrition disorders Electrolyte imbalance	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Neck pain	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Spinal cord compression	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Renal and urinary disorders Acute kidney injury	0.67% 1/150 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/150 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.

Other adverse events

Measure	Giredestrant n=150 participants at risk Participants received giredestrant, 30 mg, PO, QD, on Days 1-28 (and LHRH agonist according to clinical practice for the selected agent on Day 1 for pre/perimenopausal participants and male participants only) of each 28-day cycle until disease progression or unacceptable toxicity, whichever occurs first.	Physician's Choice of Endocrine Monotherapy n=152 participants at risk Participants received physician's choice of endocrine monotherapy (PCET; fulvestrant or aromatase inhibitor) in accordance with the local prescribing information for the respective product (and LHRH agonist according to clinical practice for the selected agent on Day 1 of each 28-day cycle for premenopausal/perimenopausal participants and male participants only) until disease progression or unacceptable toxicity, whichever occurs first.
Blood and lymphatic system disorders Anaemia	12.0% 18/150 • Number of events 19 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	9.2% 14/152 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Constipation	8.0% 12/150 • Number of events 12 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	7.9% 12/152 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Diarrhoea	10.0% 15/150 • Number of events 19 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	3.9% 6/152 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Nausea	11.3% 17/150 • Number of events 26 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	8.6% 13/152 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Gastrointestinal disorders Vomiting	10.0% 15/150 • Number of events 19 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	2.6% 4/152 • Number of events 7 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
General disorders Asthenia	8.0% 12/150 • Number of events 13 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	3.3% 5/152 • Number of events 5 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
General disorders Chest pain	6.7% 10/150 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
General disorders Fatigue	9.3% 14/150 • Number of events 18 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	5.9% 9/152 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Product dose omission in error	12.0% 18/150 • Number of events 41 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Alanine aminotransferase increased	13.3% 20/150 • Number of events 29 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	8.6% 13/152 • Number of events 14 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Aspartate aminotransferase increased	17.3% 26/150 • Number of events 34 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	11.2% 17/152 • Number of events 20 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Blood bilirubin increased	6.7% 10/150 • Number of events 18 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 2 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Metabolism and nutrition disorders Decreased appetite	6.7% 10/150 • Number of events 12 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	2.6% 4/152 • Number of events 4 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Arthralgia	12.7% 19/150 • Number of events 23 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	11.8% 18/152 • Number of events 19 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Back pain	6.0% 9/150 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	3.9% 6/152 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Bone pain	6.7% 10/150 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	6.6% 10/152 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Dizziness	7.3% 11/150 • Number of events 12 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	5.3% 8/152 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Nervous system disorders Headache	10.0% 15/150 • Number of events 20 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	9.9% 15/152 • Number of events 28 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Vascular disorders Hypertension	6.7% 10/150 • Number of events 13 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	2.0% 3/152 • Number of events 4 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Infections and infestations COVID-19	5.3% 8/150 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	6.6% 10/152 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Injury, poisoning and procedural complications Product dose omission issue	12.0% 18/150 • Number of events 44 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.00% 0/152 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Blood alkaline phosphatase increased	5.3% 8/150 • Number of events 16 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	3.3% 5/152 • Number of events 5 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Investigations Blood creatinine increased	5.3% 8/150 • Number of events 9 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	0.66% 1/152 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	3.3% 5/150 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	6.6% 10/152 • Number of events 12 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.
Vascular disorders Hot flush	6.0% 9/150 • Number of events 9 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.	5.3% 8/152 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 30 days after the final dose of study drug (duration of treatment exposure, median [range]: giredestrant: 5.5 [0.9-40.8] months and PCET: 4.6 [0.03-37.1] months). For all-cause mortality: From randomization to death from any cause (duration of follow-up for both arms, median [range]: 34.6 [0.0-41.8] months). Data collection is ongoing and AEs will be updated within 1 year of the end of trial. All-cause mortality is reported for FAS which included all participants assigned to treatment groups as randomized by the IxRS. Serious and other AEs are reported for Safety-Evaluable Set which included all participants who received at least one dose of the study treatment (giredestrant or PCET). As pre-specified in the protocol, participants were grouped according to treatment received (giredestrant or PCET) for collection of AEs.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER