Trial Outcomes & Findings for Phase 3 Trial of Elacestrant Versus Standard of Care for the Treatment of ER+/HER2- Advanced Breast Cancer (NCT NCT03778931)

Last Updated: 2025-09-15

Results Overview

Progression-free survival based on blinded IRC assessment in ESR1-mut participants defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

478 participants

Primary outcome timeframe

From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)

Results posted on

2025-09-15

Participant Flow

Participant milestones

Participant milestones
Measure	Elacestrant Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) Participants in Arm 2 will receive Investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Overall Study STARTED	239	239
Overall Study Intent-to-Treat Population	239	239
Overall Study Safety Population	237	230
Overall Study COMPLETED	152	130
Overall Study NOT COMPLETED	87	109

Reasons for withdrawal

Reasons for withdrawal
Measure	Elacestrant Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) Participants in Arm 2 will receive Investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Overall Study Withdrawal by Subject	12	25
Overall Study Physician Decision	1	3
Overall Study Participant Noncompliance	1	1
Overall Study Lost to Follow-up	4	1
Overall Study Death	69	79

Baseline Characteristics

Data was not collected for five participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Elacestrant n=239 Participants Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=239 Participants Participants in Arm 2 will receive Investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule	Total n=478 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=239 Participants	0 Participants n=239 Participants	0 Participants n=478 Participants
Age, Categorical Between 18 and 65 years	135 Participants n=239 Participants	128 Participants n=239 Participants	263 Participants n=478 Participants
Age, Categorical >=65 years	104 Participants n=239 Participants	111 Participants n=239 Participants	215 Participants n=478 Participants
Sex: Female, Male Female	233 Participants n=239 Participants	238 Participants n=239 Participants	471 Participants n=478 Participants
Sex: Female, Male Male	6 Participants n=239 Participants	1 Participants n=239 Participants	7 Participants n=478 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants n=239 Participants	18 Participants n=239 Participants	37 Participants n=478 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	194 Participants n=239 Participants	191 Participants n=239 Participants	385 Participants n=478 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	26 Participants n=239 Participants	30 Participants n=239 Participants	56 Participants n=478 Participants
Height	162.27 cm STANDARD_DEVIATION 7.860 • n=236 Participants • Data was not collected for five participants	160.97 cm STANDARD_DEVIATION 7.149 • n=237 Participants • Data was not collected for five participants	161.62 cm STANDARD_DEVIATION 7.532 • n=473 Participants • Data was not collected for five participants
Weight	72.70 kg STANDARD_DEVIATION 16.093 • n=239 Participants	72.39 kg STANDARD_DEVIATION 16.390 • n=239 Participants	72.55 kg STANDARD_DEVIATION 16.226 • n=478 Participants
Body Mass Index	27.58 kg/m^2 STANDARD_DEVIATION 5.494 • n=236 Participants • Data was not collected for five participants	27.92 kg/m^2 STANDARD_DEVIATION 5.853 • n=237 Participants • Data was not collected for five participants	27.75 kg/m^2 STANDARD_DEVIATION 5.673 • n=473 Participants • Data was not collected for five participants
Eastern Cooperative Oncology Group Performance Status 0: Fully active, able to carry on all pre-disease performance without restriction	143 Participants n=239 Participants	135 Participants n=239 Participants	278 Participants n=478 Participants
Eastern Cooperative Oncology Group Performance Status 1: Restricted in physically strenuous activity but ambulatory & can carry out light, sedentary work	96 Participants n=239 Participants	103 Participants n=239 Participants	199 Participants n=478 Participants
Eastern Cooperative Oncology Group Performance Status 2: Ambulatory and capable of all selfcare but unable to carry out any work activities	0 Participants n=239 Participants	1 Participants n=239 Participants	1 Participants n=478 Participants

PRIMARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)

Outcome measures

Outcome measures
Measure	Elacestrant n=115 Participants Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=113 Participants Participants in Arm 2 will receive investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Progression-free Survival in ESR1-mut Participants	3.78 months Interval 2.17 to 7.26	1.87 months Interval 1.87 to 2.14

PRIMARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)

Progression-free survival based on blinded imaging review committee (IRC) assessment in all (ESR1-mut and ESR1-wt) participants.

Outcome measures

Outcome measures
Measure	Elacestrant n=239 Participants Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=239 Participants Participants in Arm 2 will receive investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Progression-free Survival in All Participants	2.79 months Interval 1.94 to 3.78	1.91 months Interval 1.87 to 2.1

SECONDARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)

Overall survival in ESR1-mut participants, where overall survival is defined as the length of time from randomization until the date of death from any cause.

Outcome measures

Outcome measures
Measure	Elacestrant n=115 Participants Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=113 Participants Participants in Arm 2 will receive investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Overall Survival in ESR1-mut Participants	NA months Interval 18.6 to NA=not calculable (insufficient number of participants with events)	16.95 months Interval 14.0 to NA=not calculable (insufficient number of participants with events)

SECONDARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)

Overall survival in all (ESR1-mut and ESR1-wt) participants.

Outcome measures

Outcome measures
Measure	Elacestrant n=239 Participants Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=239 Participants Participants in Arm 2 will receive investigator's choice of one of the standard-of-care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Overall Survival in All Participants	NA months Interval 19.29 to NA=not calculable (insufficient number of participants with events)	NA months Interval 15.8 to NA=not calculable (insufficient number of participants with events)

Adverse Events

Elacestrant

Serious events: 29 serious events

Other events: 215 other events

Deaths: 70 deaths

Standard of Care (SoC)

Serious events: 25 serious events

Other events: 195 other events

Deaths: 80 deaths

Serious adverse events

Other adverse events

Additional Information

Carlos A. Garay, MD, Senior Vice President, Clinical Development & Medical Affairs - Solid Tumors

Stemline Therapeutics, Inc.

Phone: +1-877-332-7967

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Elacestrant n=237 participants at risk Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=230 participants at risk Participants in Arm 2 will receive Investigator's choice of one of the Standard-of-Care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Blood and lymphatic system disorders Antiphospholipid syndrome	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Nausea	1.3% 3/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Vomiting	0.84% 2/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Small intestinal obstruction	0.84% 2/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Abdominal pain	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.87% 2/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Colitis	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Diarrhoea	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Enteritis	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Ileus	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders General physical health deterioration	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Pyrexia	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Hepatobiliary disorders Cholecystitis acute	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Diverticulitis	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Pneumonia	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	1.3% 3/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Septic shock	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations COVID-19	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Device related sepsis	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Sepsis	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Urinary tract infection	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.87% 2/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Blood bilirubin increased	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Neutrophil count decreased	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Platelet count decreased	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Renal and urinary disorders Acute kidney injury	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Cardiac disorders Cardiac arrest	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Cardiac disorders Angina pectoris	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Cardiac disorders Arrhythmia	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Cardiac disorders Myocardial infarction	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Intestinal ischaemia	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Asthenia	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Mucosal inflammation	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Gait disturbance	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Injury, poisoning and procedural complications Femoral neck fracture	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Injury, poisoning and procedural complications Road traffic accident	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Decreased appetite	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Dehydration	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Electrolyte imbalance	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Hypercalcaemia	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.43% 1/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Back pain	0.84% 2/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Bone pain	0.42% 1/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	0.00% 0/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.

Other adverse events
Measure	Elacestrant n=237 participants at risk Participants in Arm 1 will receive elacestrant Elacestrant: 400 mg/day once daily oral dosing	Standard of Care (SoC) n=230 participants at risk Participants in Arm 2 will receive Investigator's choice of one of the Standard-of-Care drugs (fulvestrant, anastrozole, letrozole, or exemestane) Standard of Care: * Fulvestrant: 500 mg administered intramuscularly (IM) into the buttocks as two 5 mL injections on C1D1, C1D15 and C2D1 and Day 1 of every subsequent 28-day cycle * Anastrozole 1 mg/day on a continuous dosing schedule * Letrozole: 2.5 mg/day on a continuous dosing schedule * Exemestane: 25 mg/day on a continuous dosing schedule
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.6% 11/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.7% 13/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Myalgia	4.6% 11/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	7.4% 17/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Blood and lymphatic system disorders Anaemia	9.3% 22/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	7.4% 17/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Nausea	35.0% 83/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	19.1% 44/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Vomiting	19.0% 45/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	8.7% 20/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Diarrhoea	13.9% 33/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	9.6% 22/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Constipation	12.2% 29/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	6.5% 15/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Dyspepsia	10.1% 24/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	2.6% 6/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Gastrointestinal disorders Abdominal pain	6.3% 15/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.7% 13/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Fatigue	19.0% 45/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	19.1% 44/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Asthenia	8.9% 21/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	8.3% 19/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
General disorders Injection site pain	0.00% 0/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	6.1% 14/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Infections and infestations Urinary tract infection	6.8% 16/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.2% 12/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Aspartate aminotransferase increased	13.1% 31/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	12.6% 29/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Alanine aminotransferase increased	9.3% 22/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	10.4% 24/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Investigations Blood alkaline phosphatase increased	6.3% 15/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	7.4% 17/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Decreased appetite	14.8% 35/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	9.6% 22/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 34/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	16.1% 37/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Back pain	13.5% 32/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	9.6% 22/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.9% 14/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	3.0% 7/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Nervous system disorders Headache	12.2% 29/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	11.3% 26/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Psychiatric disorders Insomnia	7.6% 18/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	4.8% 11/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.6% 18/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	7.0% 16/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Respiratory, thoracic and mediastinal disorders Cough	6.3% 15/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.2% 12/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Vascular disorders Hot flush	11.4% 27/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	8.3% 19/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Pain in extremity	7.6% 18/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	6.1% 14/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Musculoskeletal and connective tissue disorders Bone pain	5.9% 14/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	6.5% 15/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Metabolism and nutrition disorders Hyperglycaemia	2.5% 6/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.2% 12/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.
Vascular disorders Hypertension	3.8% 9/237 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.	5.2% 12/230 • 24 months All-Cause Mortality, Progression-free Survival, and Overall Survival were assessed with the Intention-to-Treat Population, which consisted of all randomized participants. Adverse Events (Serious and Other) reporting reflects the Safety Population, which consisted of all participants who received at least 1 dose of study medication. All deaths regardless of causality are reported in the All-Cause Mortality section. Only deaths leading to study discontinuation are reported in the Participant Flow.