Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (NCT NCT02107703)

NCT ID: NCT02107703

Last Updated: 2025-10-21

Results Overview

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 669 participants
• Primary outcome timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)
• Results posted on: 2025-10-21

Participant Flow

With Overall Survival (OS) as a key outcome, participants who completed included those who died due to any cause and those who were off treatment, alive and in follow-up at the time of the final OS analysis.

Participant milestones

Measure	Abemaciclib + Fulvestrant Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Overall Study STARTED	446	223
Overall Study Received at Least 1 Dose of Study Drug	441	223
Overall Study COMPLETED	332	188
Overall Study NOT COMPLETED	114	35

Reasons for withdrawal

Measure	Abemaciclib + Fulvestrant Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Overall Study Withdrawal by Subject	46	21
Overall Study Lost to Follow-up	20	9
Overall Study On study treatment/follow up	48	5

Baseline Characteristics

All randomized participants who had baseline Ethnicity data.

Baseline characteristics by cohort

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Total n=669 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 11.2 • n=446 Participants	61.1 years STANDARD_DEVIATION 11.7 • n=223 Participants	59.9 years STANDARD_DEVIATION 11.4 • n=669 Participants
Sex: Female, Male Female	446 Participants n=446 Participants	223 Participants n=223 Participants	669 Participants n=669 Participants
Sex: Female, Male Male	0 Participants n=446 Participants	0 Participants n=223 Participants	0 Participants n=669 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	57 Participants n=443 Participants • All randomized participants who had baseline Ethnicity data.	25 Participants n=223 Participants • All randomized participants who had baseline Ethnicity data.	82 Participants n=666 Participants • All randomized participants who had baseline Ethnicity data.
Ethnicity (NIH/OMB) Not Hispanic or Latino	303 Participants n=443 Participants • All randomized participants who had baseline Ethnicity data.	162 Participants n=223 Participants • All randomized participants who had baseline Ethnicity data.	465 Participants n=666 Participants • All randomized participants who had baseline Ethnicity data.
Ethnicity (NIH/OMB) Unknown or Not Reported	83 Participants n=443 Participants • All randomized participants who had baseline Ethnicity data.	36 Participants n=223 Participants • All randomized participants who had baseline Ethnicity data.	119 Participants n=666 Participants • All randomized participants who had baseline Ethnicity data.
Race (NIH/OMB) American Indian or Alaska Native	18 Participants n=446 Participants	8 Participants n=223 Participants	26 Participants n=669 Participants
Race (NIH/OMB) Asian	149 Participants n=446 Participants	65 Participants n=223 Participants	214 Participants n=669 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=446 Participants	0 Participants n=223 Participants	0 Participants n=669 Participants
Race (NIH/OMB) Black or African American	9 Participants n=446 Participants	5 Participants n=223 Participants	14 Participants n=669 Participants
Race (NIH/OMB) White	237 Participants n=446 Participants	136 Participants n=223 Participants	373 Participants n=669 Participants
Race (NIH/OMB) More than one race	0 Participants n=446 Participants	0 Participants n=223 Participants	0 Participants n=669 Participants
Race (NIH/OMB) Unknown or Not Reported	33 Participants n=446 Participants	9 Participants n=223 Participants	42 Participants n=669 Participants
Region of Enrollment North America	120 Participants n=446 Participants	58 Participants n=223 Participants	178 Participants n=669 Participants
Region of Enrollment Europe	179 Participants n=446 Participants	100 Participants n=223 Participants	279 Participants n=669 Participants
Region of Enrollment Taiwan	25 Participants n=446 Participants	14 Participants n=223 Participants	39 Participants n=669 Participants
Region of Enrollment Japan	64 Participants n=446 Participants	31 Participants n=223 Participants	95 Participants n=669 Participants
Region of Enrollment South Korea	58 Participants n=446 Participants	20 Participants n=223 Participants	78 Participants n=669 Participants

PRIMARY outcome

Timeframe: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Population: All randomized participants. Censored participants: Abemaciclib=224.

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Progression-Free Survival (PFS)	16.4 Months Interval 14.4 to 19.3	9.3 Months Interval 7.4 to 11.4

SECONDARY outcome

Timeframe: From Date of Randomization until Death Due to Any Cause (Up To 72 Months)

Population: All randomized participants. Censored participants: Abemaciclib=163 (36.5%), Placebo = 66 (29.6).

OS defined as the time from the date of randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The final analysis of the OS outcome was conducted after 440 OS events had been observed.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Overall Survival (OS)	45.80 Months Interval 38.96 to 52.64	37.25 Months Interval 34.36 to 43.2

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Population: All randomized participants.

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	35.2 Percentage of participants Interval 30.8 to 39.6	16.1 Percentage of participants Interval 11.3 to 21.0

SECONDARY outcome

Timeframe: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Population: All randomized participants with response.

DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=157 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=36 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Duration of Response (DOR)	NA Months Interval 18.05 to The median DoR for participants has not been reached.	25.6 Months Interval 11.9 to 25.6

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Population: All randomized participants.

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	83.0 Percentage of participants Interval 79.5 to 86.4	75.8 Percentage of participants Interval 70.2 to 81.4

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Population: All randomized participants.

Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions.PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants=(participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) *100.PD was at least a 20% increase in sum of the diameters of target lesions,with reference being the smallest sum on study and an absolute increase of at least 5 mm or unequivocal progression of non-target lesions,or 1 or more new lesions.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=446 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])	72.2 Percentage of participants Interval 68.0 to 76.4	56.1 Percentage of participants Interval 49.5 to 62.6

SECONDARY outcome

Timeframe: Baseline, End of Study (Up To 31 Months)

Population: All randomized participants who received at least one dose of study drug with a baseline and at least 1 post-baseline result.

A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=441 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)	-0.06 score on a scale Standard Error 0.07	0.00 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose

Population: All randomized participants who received at least one dose of 150 mg study drug (Abemaciclib) with evaluable Abemaciclib, M2 and M20 PK data.

Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=326 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 M2	1640 Nanograms*hour/milliliters (ng*h/mL) Geometric Coefficient of Variation 70.2	—
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 Abemaciclib	2960 Nanograms*hour/milliliters (ng*h/mL) Geometric Coefficient of Variation 32.2	—
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 M20	2870 Nanograms*hour/milliliters (ng*h/mL) Geometric Coefficient of Variation 69.6	—

SECONDARY outcome

Timeframe: Baseline, End of Study (Up To 31 Months)

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.

European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=441 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=223 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)	0.12 mm Standard Error 0.65	1.16 mm Standard Error 0.92

SECONDARY outcome

Timeframe: Baseline, Short Term Follow Up (Up To 31 Months)

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data at short term follow up for each EORTC QLQ-C30 items.

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=180 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=126 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global health status	-4.57 units on a scale Standard Error 1.55	-8.15 units on a scale Standard Error 1.87
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional scale: Physical functioning	-3.76 units on a scale Standard Error 1.29	-7.59 units on a scale Standard Error 1.59
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional scale: Role functioning	-4.87 units on a scale Standard Error 1.73	-9.58 units on a scale Standard Error 2.12
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional scale: Emotional functioning	2.38 units on a scale Standard Error 1.38	-2.44 units on a scale Standard Error 1.70
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional scale: Cognitive functioning	-3.16 units on a scale Standard Error 1.29	-2.96 units on a scale Standard Error 1.58
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional scale: Social functioning	-4.62 units on a scale Standard Error 1.61	-4.78 units on a scale Standard Error 1.97
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Fatigue	5.01 units on a scale Standard Error 1.45	7.83 units on a scale Standard Error 1.78
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Pain	-0.47 units on a scale Standard Error 1.82	4.38 units on a scale Standard Error 2.21
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Dyspnoea	5.21 units on a scale Standard Error 1.70	5.39 units on a scale Standard Error 2.10
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Insomnia	-0.04 units on a scale Standard Error 1.86	3.76 units on a scale Standard Error 2.27
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Appetite loss	2.06 units on a scale Standard Error 1.85	6.40 units on a scale Standard Error 2.23
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Constipation	-0.15 units on a scale Standard Error 1.59	3.79 units on a scale Standard Error 1.92
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Diarrhoea	4.14 units on a scale Standard Error 1.66	2.67 units on a scale Standard Error 1.99
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Financial difficulties	0.34 units on a scale Standard Error 1.60	2.85 units on a scale Standard Error 1.96
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Symptom scale: Nausea and vomiting	2.81 units on a scale Standard Error 1.35	6.49 units on a scale Standard Error 1.64

SECONDARY outcome

Timeframe: Baseline, Short Term Follow Up (Up To 31 Months)

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-BR23 data at short term follow up for each BR23 items.

EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Outcome measures

Measure	Abemaciclib + Fulvestrant n=182 Participants Abemaciclib 150 mg administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.	Placebo + Fulvestrant n=126 Participants Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Functional scale: Body image	-2.20 Units on a scale Standard Error 1.46	-3.27 Units on a scale Standard Error 1.83
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Functional scale:Sexual functioning	0.41 Units on a scale Standard Error 1.00	-1.60 Units on a scale Standard Error 1.25
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Functional scale: Future perspective	6.06 Units on a scale Standard Error 2.06	10.05 Units on a scale Standard Error 2.51
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Symptom scale: Systemic therapy side effects	7.23 Units on a scale Standard Error 1.00	6.98 Units on a scale Standard Error 1.22
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Symptom scale: Breast symptoms	-2.10 Units on a scale Standard Error 0.89	-0.96 Units on a scale Standard Error 1.09
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Symptom scale: Arm symptoms	-0.45 Units on a scale Standard Error 1.29	0.10 Units on a scale Standard Error 1.59

Adverse Events

Abemaciclib + Fulvestrant

Serious events: 129 serious events

Other events: 432 other events

Deaths: 283 deaths

Placebo + Fulvestrant

Serious events: 33 serious events

Other events: 194 other events

Deaths: 157 deaths

Serious adverse events

Measure	Abemaciclib + Fulvestrant n=441 participants at risk 150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo + Fulvestrant n=223 participants at risk Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Infections and infestations Kidney infection	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Lower respiratory tract infection	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Cellulitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Covid-19	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Enterocolitis infectious	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Gastroenteritis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Anaemia	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Febrile neutropenia	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Neutropenia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Pancytopenia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Atrial fibrillation	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Atrioventricular block first degree	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Cardiac arrest	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Cardiac failure	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Myocardial infarction	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Restrictive cardiomyopathy	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Sinus tachycardia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Supraventricular tachycardia	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Cardiac disorders Ventricular tachycardia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Ear and labyrinth disorders Middle ear inflammation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Endocrine disorders Adrenal insufficiency	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Eye disorders Macular hole	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Abdominal pain	1.1% 5/441 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Ascites	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Diarrhoea	2.0% 9/441 • Number of events 9 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Enterocolitis	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Gastritis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Gastrointestinal amyloidosis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Intestinal obstruction	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Nausea	1.1% 5/441 • Number of events 5 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.90% 2/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Oesophageal pain	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Pancreatitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Small intestinal perforation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Volvulus	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Vomiting	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Injection site reaction	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Localised oedema	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Malaise	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Multiple organ dysfunction syndrome	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Non-cardiac chest pain	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Oedema peripheral	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Pain	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Pyrexia	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Surgical failure	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Hepatobiliary disorders Cholangitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Hepatobiliary disorders Cholecystitis	0.91% 4/441 • Number of events 4 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Hepatobiliary disorders Drug-induced liver injury	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Hepatobiliary disorders Hepatic failure	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Hepatobiliary disorders Hepatic function abnormal	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Immune system disorders Autoimmune disorder	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Immune system disorders Hypersensitivity	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Immune system disorders Sarcoidosis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Bartholin's abscess	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Bronchitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Lymph gland infection	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Mastitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Osteomyelitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Periorbital cellulitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Pneumonia	2.9% 13/441 • Number of events 13 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Pyelonephritis acute	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Salmonella bacteraemia	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Sepsis	1.4% 6/441 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Skin infection	1.4% 6/441 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Upper respiratory tract infection	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Urinary tract infection	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Ankle fracture	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Fall	0.68% 3/441 • Number of events 4 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Fracture	1.8% 8/441 • Number of events 8 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Limb injury	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Spinal fracture	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Wound complication	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Injury, poisoning and procedural complications Wrist fracture	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Alanine aminotransferase increased	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Aspartate aminotransferase increased	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood alkaline phosphatase increased	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood bilirubin increased	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood creatinine increased	0.91% 4/441 • Number of events 4 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood follicle stimulating hormone abnormal	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Electrocardiogram qt prolonged	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations General physical condition abnormal	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Hormone level abnormal	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Oestradiol abnormal	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Decreased appetite	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Dehydration	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hypercalcaemia	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hyperglycaemia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hypocalcaemia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hypokalaemia	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Arthritis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Back pain	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.90% 2/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Bone pain	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 5/441 • Number of events 5 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Myositis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign bone neoplasm	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Cerebrovascular accident	0.91% 4/441 • Number of events 4 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Depressed level of consciousness	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.90% 2/223 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Dizziness	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Headache	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Neuropathy	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Syncope	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Confusional state	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Psychotic disorder	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Suicidal ideation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Renal and urinary disorders Acute kidney injury	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Renal and urinary disorders Chronic kidney disease	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Renal and urinary disorders Nephrolithiasis	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Renal and urinary disorders Urinary retention	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Reproductive system and breast disorders Pelvic pain	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/441 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Cough	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 6/441 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.90% 2/223 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.45% 2/441 • Number of events 2 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.7% 6/223 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.68% 3/441 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Rash	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Surgical and medical procedures Fracture treatment	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Surgical and medical procedures Internal fixation of fracture	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Surgical and medical procedures Leg amputation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Surgical and medical procedures Medical device implantation	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Embolism	2.0% 9/441 • Number of events 11 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Hypertension	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Lymphoedema	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Vasculitis	0.23% 1/441 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.00% 0/223 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.

Other adverse events

Measure	Abemaciclib + Fulvestrant n=441 participants at risk 150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo + Fulvestrant n=223 participants at risk Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
Blood and lymphatic system disorders Anaemia	35.1% 155/441 • Number of events 313 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.9% 11/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Leukopenia	33.6% 148/441 • Number of events 500 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	1.8% 4/223 • Number of events 10 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Lymphopenia	10.2% 45/441 • Number of events 113 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.90% 2/223 • Number of events 9 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Neutropenia	49.7% 219/441 • Number of events 760 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	3.6% 8/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Blood and lymphatic system disorders Thrombocytopenia	17.9% 79/441 • Number of events 135 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.7% 6/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Eye disorders Lacrimation increased	7.7% 34/441 • Number of events 44 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	1.3% 3/223 • Number of events 3 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Abdominal distension	5.4% 24/441 • Number of events 28 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.2% 5/223 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Abdominal pain	37.6% 166/441 • Number of events 320 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	16.1% 36/223 • Number of events 65 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Constipation	16.6% 73/441 • Number of events 96 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	16.1% 36/223 • Number of events 47 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Diarrhoea	87.1% 384/441 • Number of events 1205 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	27.8% 62/223 • Number of events 104 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Dry mouth	7.9% 35/441 • Number of events 40 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	6.7% 15/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Dyspepsia	7.5% 33/441 • Number of events 43 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	5.4% 12/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.7% 25/441 • Number of events 27 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.2% 5/223 • Number of events 5 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Nausea	49.4% 218/441 • Number of events 367 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	24.7% 55/223 • Number of events 72 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Stomatitis	18.6% 82/441 • Number of events 119 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	10.8% 24/223 • Number of events 30 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Gastrointestinal disorders Vomiting	29.5% 130/441 • Number of events 253 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	11.7% 26/223 • Number of events 43 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Chills	5.9% 26/441 • Number of events 30 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Fatigue	43.5% 192/441 • Number of events 294 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	28.7% 64/223 • Number of events 81 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Influenza like illness	9.3% 41/441 • Number of events 71 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 23 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Injection site reaction	10.9% 48/441 • Number of events 66 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	9.9% 22/223 • Number of events 40 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Oedema peripheral	14.1% 62/441 • Number of events 83 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 21 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Pain	6.8% 30/441 • Number of events 42 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.9% 11/223 • Number of events 14 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
General disorders Pyrexia	14.1% 62/441 • Number of events 99 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 18 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Sinusitis	5.4% 24/441 • Number of events 36 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.7% 6/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Skin infection	5.7% 25/441 • Number of events 36 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.7% 6/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Upper respiratory tract infection	20.0% 88/441 • Number of events 159 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	8.5% 19/223 • Number of events 32 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Infections and infestations Urinary tract infection	10.4% 46/441 • Number of events 76 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.5% 10/223 • Number of events 18 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Alanine aminotransferase increased	17.9% 79/441 • Number of events 138 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	5.4% 12/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Aspartate aminotransferase increased	18.4% 81/441 • Number of events 132 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 25 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood alkaline phosphatase increased	6.1% 27/441 • Number of events 47 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	3.1% 7/223 • Number of events 10 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Blood creatinine increased	14.3% 63/441 • Number of events 134 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Investigations Weight decreased	12.2% 54/441 • Number of events 65 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	3.1% 7/223 • Number of events 10 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Decreased appetite	28.8% 127/441 • Number of events 162 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	13.5% 30/223 • Number of events 31 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Metabolism and nutrition disorders Hypokalaemia	9.3% 41/441 • Number of events 77 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	3.1% 7/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Arthralgia	17.7% 78/441 • Number of events 154 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	15.2% 34/223 • Number of events 47 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Back pain	14.1% 62/441 • Number of events 100 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	13.5% 30/223 • Number of events 40 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Bone pain	6.6% 29/441 • Number of events 36 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	9.4% 21/223 • Number of events 25 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Muscular weakness	12.0% 53/441 • Number of events 90 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	6.7% 15/223 • Number of events 19 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 44/441 • Number of events 57 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	6.3% 14/223 • Number of events 17 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Musculoskeletal and connective tissue disorders Pain in extremity	11.8% 52/441 • Number of events 119 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.9% 11/223 • Number of events 13 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Dizziness	15.2% 67/441 • Number of events 111 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 18 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Dysgeusia	18.6% 82/441 • Number of events 106 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.7% 6/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Headache	24.5% 108/441 • Number of events 203 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	16.1% 36/223 • Number of events 67 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Nervous system disorders Neuropathy	9.5% 42/441 • Number of events 51 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	9.4% 21/223 • Number of events 26 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Anxiety	5.2% 23/441 • Number of events 26 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.2% 5/223 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Depression	5.9% 26/441 • Number of events 28 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.5% 10/223 • Number of events 12 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Psychiatric disorders Insomnia	9.5% 42/441 • Number of events 53 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	9.4% 21/223 • Number of events 24 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Cough	17.7% 78/441 • Number of events 114 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	13.5% 30/223 • Number of events 35 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.6% 51/441 • Number of events 58 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	10.3% 23/223 • Number of events 28 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.3% 28/441 • Number of events 32 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	6.3% 14/223 • Number of events 15 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Alopecia	17.2% 76/441 • Number of events 88 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	1.8% 4/223 • Number of events 4 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Dermatitis acneiform	5.2% 23/441 • Number of events 29 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.2% 5/223 • Number of events 6 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Dry skin	10.9% 48/441 • Number of events 61 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	2.2% 5/223 • Number of events 7 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Pruritus	14.5% 64/441 • Number of events 82 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	7.2% 16/223 • Number of events 18 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Skin and subcutaneous tissue disorders Rash	12.2% 54/441 • Number of events 75 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	4.9% 11/223 • Number of events 13 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Embolism	5.9% 26/441 • Number of events 31 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	0.45% 1/223 • Number of events 1 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Hot flush	11.6% 51/441 • Number of events 71 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	11.2% 25/223 • Number of events 28 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.
Vascular disorders Lymphoedema	5.2% 23/441 • Number of events 25 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.	1.8% 4/223 • Number of events 5 • Up To 7 years 7.7 Months Adverse Events: All randomized participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants. Analyses presented in this report are based on a database lock for the pre-planned final OS analysis of 22 April 2022.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60