A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer (MONARCH 3)

• ClinicalTrials.gov Identifier: NCT02246621
• Recruitment Status: Active, not recruiting
• First Posted: September 23, 2014
• Results First Posted: March 23, 2018
• Last Update Posted: September 10, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Drug: Abemaciclib; Drug: Anastrozole; Drug: Letrozole; Drug: Placebo
• Enrollment: 493

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Abemaciclib + NSAI (Nonsteroidal Aromatase Inhibitors)	Placebo + NSAI
Arm/Group Description	150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Period Title: Overall Study
Started	328	165
Received At Least One Dose of Study Drug	326	162
Completed	32	17
Not Completed	296	148
Reason Not Completed
Withdrawal by Subject	36	14
Lost to Follow-up	3	1
On Study Treatment/ Follow Up	257	133

Baseline Characteristics

Arm/Group Title		Abemaciclib + NSAI	Placebo + NSAI	Total
Arm/Group Description		150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Total of all reporting groups
Overall Number of Baseline Participants		328	165	493
Baseline Analysis Population Description		All randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	328 participants	165 participants	493 participants
		63.13 (9.92)	62.92 (9.96)	63.05 (9.92)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	165 participants	493 participants
	Female	328	165	493
	Male	0	0	0
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	165 participants	493 participants
	Hispanic or Latino	32	12	44
	Not Hispanic or Latino	230	125	355
	Unknown or Not Reported	66	28	94
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	328 participants	165 participants	493 participants
	American Indian or Alaska Native	4	3	7
	Asian	103	45	148
	Native Hawaiian or Other Pacific Islander	0	1	1
	Black or African American	5	3	8
	White	186	102	288
	More than one race	2	0	2
	Unknown or Not Reported	28	11	39
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	328 participants	165 participants	493 participants
Australia		9	6	15
Austria		10	3	13
Belgium		14	7	21
Canada		14	11	25
Germany		11	5	16
Spain		16	14	30
France		30	11	41
United Kingdom		7	2	9
Greece		0	1	1
Israel		28	19	47
Italy		11	11	22
Japan		38	15	53
South Korea		41	18	59
Mexico		22	7	29
Netherlands		2	4	6
New Zealand		1	0	1
Russia		13	6	19
Slovakia		2	0	2
Sweden		3	1	4
Turkey		9	3	12
Taiwan		23	9	32
United States		24	12	36

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by 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.
Time Frame	Randomization to Progressive Disease or Death Due to Any Cause (Up to 26 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	328	165
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	14.73; (11.11 to 17.46)

[1]

Median of PFS not reached due to number of events not yet attained. Anticipated reporting date: April 2018

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abemaciclib + NSAI, Placebo + NSAI
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.000021
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.543
	Confidence Interval	(2-Sided) 95%; 0.409 to 0.723
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS defined as the time from first dose date 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.
Time Frame	Randomization to Progressive Disease or Death Due to Any Cause (Estimated Up to 82 Months)

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Description	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.
Time Frame	Randomization to Progressive Disease or Death Due to Any Cause (Up to 26 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	328	165
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	48.2; (42.8 to 53.6)	34.5; (27.3 to 41.8)

4. Secondary Outcome

Title	Duration of Response (DoR)
Description	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.
Time Frame	CR or PR to Disease Progression or Death Due to Any Cause (Up to 26 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and first evidence of CR or PR as assessed by the investigator.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	158	57
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	14.1 [1]; (11.08 to NA)

[1]

DoR not reached due to number of events not yet attained. Anticipated reporting date: April 2018

5. Secondary Outcome

Title	Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])
Description	DCR was the percentage of participants with a best overall response of CR, PR, or 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.
Time Frame	Randomization to Progressive Disease or Death Due to Any Cause (Up to 26 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	328	165
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	88.7; (85.3 to 92.1)	86.7; (81.5 to 91.9)

6. Secondary Outcome

Title	Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR])
Description	CBR defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months. CR, PR, or SD were defined 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. Percentage of participants = (participants with CR+PR+SD with a duration of at least 6 months / number of participants enrolled) * 100.
Time Frame	Randomization to Progressive Disease or Death Due to Any Cause (Up to 26 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	328	165
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	78.0; (73.6 to 82.5)	71.5; (64.6 to 78.4)

7. Secondary Outcome

Title	Change From Baseline to End of Study in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional Scale Scores
Description	EORTC QLQ-C30 v3.0 is 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. Functional scale options are defined on a 7-point scale ranging from 1, "Very poor" to 7, "Excellent". A linear transformation is applied to standardize the raw scores to range between 0 and 100. For functional domains and global health status, higher scores represent a better level of functioning. Best change from baseline results determined by Least Square (LS) mean estimated with randomization stratification factors and baseline value as continuous covariate. EORTC change score definitions are described in Cocks et al, (2012) and differ for each item. Small changes are generally defined as at least a 3, 4 or 5 point change from baseline.
Time Frame	Baseline, End of Study (Estimated up to 34 Months)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Efficacy data were analyzed based upon the interim analysis as described in the study design. This outcome measure is from baseline to end of study and will be analyzed and reported after the end of study data are collected. Anticipated reporting December 2018.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Secondary Outcome

Title	Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores
Description	EORTC QLQ-C30 v3.0 is 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. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For symptoms scales, higher scores represented a greater degree of symptoms. Best change from baseline results determined by Least Square (LS) mean estimated with randomization stratification factors and baseline value as continuous covariate. EORTC change score definitions are described in Cocks et al, (2012) and differ according to each item. Small changes are generally defined as at least a 3, 4 or 5 point change from baseline
Time Frame	Baseline, End of Study (Estimated up to 34 Months)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Efficacy data were analyzed based upon the interim analysis as described in the study design. This outcome measure is from baseline to end of study and will be analyzed and reported after the end of study data are collected. Anticipated reporting December 2018.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

9. Secondary Outcome

Title	Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire
Description	The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much" . All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.
Time Frame	Baseline, End of Study (Estimated up to 34 Months)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Efficacy data were analyzed based upon the interim analysis as described in the study design. This outcome measure is from baseline to end of study and will be analyzed and reported after the end of study data are collected. Anticipated reporting December 2018.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

10. Secondary Outcome

Title	Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L)
Description	The EuroQol-5D (version 5L) is a brief self-administered, validated instrument consisting of 2 parts.The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a five level scale (no problem, slight problem, moderate problem, severe problem and extreme problem) with higher levels indicating greater severity/ impairment. Published weights are available that allow for the creation of a single summary score called the EQ-5D index that ranges from 0 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health. Minimally important differences in the EQ-5D index score are 0.06 or greater in cancer patients, per Pickard et al (2007).
Time Frame	Baseline, End of Study (Estimated up to 34 Months)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Efficacy data were analyzed based upon the interim analysis as described in the study design. This outcome measure is from baseline to end of study and will be analyzed and reported after the end of study data are collected. Anticipated reporting December 2018.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

11. Secondary Outcome

Title	Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale
Description	The EuroQol-5D (version 5L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). Minimally important differences in the EQ-5D VAS score are 7 or greater in cancer patients, per Pickard et al (2007).
Time Frame	Baseline, End of Study (Estimated up to 34 Months)

Outcome Measure Data

Analysis Population Description

Zero participants analyzed. Efficacy data were analyzed based upon the interim analysis as described in the study design. This outcome measure is from baseline to end of study and will be analyzed and reported after the end of study data are collected. Anticipated reporting December 2018.

Arm/Group Title	Abemaciclib + NSAI	Placebo + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).	Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

12. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity [AUC(0-∞)] of Abemaciclib and Its Metabolites M2 and M20
Description	[Not Specified]
Time Frame	Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with evaluable PK data.

Arm/Group Title	Abemaciclib + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	322
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram*hours/milliliter (ng*h/mL)
Abemaciclib	3360; (36.6%)
M2	1290; (75.8%)
M20	2300; (74.4%)

13. Secondary Outcome

Title	PK: Hepatic Clearance of Abemaciclib, and Apparent Hepatic Clearance of Its Metabolites M2 and M20
Description	[Not Specified]
Time Frame	Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with evaluable PK data.

Arm/Group Title	Abemaciclib + NSAI
Arm/Group Description:	150 mg Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
Overall Number of Participants Analyzed	322
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: liters/hour (L/h)
Abemaciclib	23.0; (26.7%)
M2	21.6; (50.4%)
M20	26.0; (46.4%)

Adverse Events

Time Frame	Entire study; up to 34 months
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Abemaciclib + NSAI		Placebo + NSAI
Arm/Group Description	150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).		Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
All-Cause Mortality
	Abemaciclib + NSAI		Placebo + NSAI
	Affected / at Risk (%)		Affected / at Risk (%)
Total	32/327 (9.79%)		16/161 (9.94%)
Serious Adverse Events
	Abemaciclib + NSAI		Placebo + NSAI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/327 (27.52%)		24/161 (14.91%)
Blood and lymphatic system disorders
Anaemia † 1	5/327 (1.53%)	5	0/161 (0.00%)	0
Disseminated intravascular coagulation † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Neutropenia † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Cardiac disorders
Angina pectoris † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Atrial fibrillation † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Atrial tachycardia † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Cardiac failure † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Myocardial infarction † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Pericardial effusion † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Stress cardiomyopathy † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Supraventricular tachycardia † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Ventricular arrhythmia † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Vertigo positional † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Colitis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Constipation † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Diarrhoea † 1	5/327 (1.53%)	7	0/161 (0.00%)	0
Enterocolitis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Food poisoning † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Ileus † 1	1/327 (0.31%)	1	1/161 (0.62%)	1
Nausea † 1	1/327 (0.31%)	2	0/161 (0.00%)	0
Oesophagitis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Rectal haemorrhage † 1	1/327 (0.31%)	1	1/161 (0.62%)	1
Vomiting † 1	2/327 (0.61%)	3	2/161 (1.24%)	2
General disorders
General physical health deterioration † 1	2/327 (0.61%)	2	1/161 (0.62%)	2
Pyrexia † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Sudden death † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Ulcer haemorrhage † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Hepatobiliary disorders
Cholecystitis † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Hepatitis toxic † 1	1/327 (0.31%)	2	0/161 (0.00%)	0
Immune system disorders
Anaphylactic reaction † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Infections and infestations
Cellulitis † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Erysipelas † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Gastroenteritis † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Lung infection † 1	9/327 (2.75%)	12	0/161 (0.00%)	0
Mastitis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Periodontitis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Sepsis † 1	1/327 (0.31%)	1	1/161 (0.62%)	1
Skin infection † 1	1/327 (0.31%)	2	1/161 (0.62%)	1
Urinary tract infection † 1	3/327 (0.92%)	3	1/161 (0.62%)	1
Wound infection † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Injury, poisoning and procedural complications
Ankle fracture † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Fall † 1	1/327 (0.31%)	1	1/161 (0.62%)	1
Fracture † 1	2/327 (0.61%)	2	1/161 (0.62%)	1
Hip fracture † 1	3/327 (0.92%)	3	0/161 (0.00%)	0
Spinal fracture † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Wound dehiscence † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Wrist fracture † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Investigations
Alanine aminotransferase increased † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Aspartate aminotransferase increased † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Blood bilirubin increased † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Blood creatinine increased † 1	3/327 (0.92%)	3	0/161 (0.00%)	0
Metabolism and nutrition disorders
Cachexia † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Decreased appetite † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Dehydration † 1	4/327 (1.22%)	5	2/161 (1.24%)	2
Hypercalcaemia † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Hyperkalaemia † 1	2/327 (0.61%)	2	0/161 (0.00%)	0
Hyponatraemia † 1	2/327 (0.61%)	3	0/161 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Arthritis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Back pain † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Bone pain † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Breast cancer metastatic † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Tumour haemorrhage † 1	0/327 (0.00%)	0	1/161 (0.62%)	1
Nervous system disorders
Cerebral ischaemia † 1	1/327 (0.31%)	2	0/161 (0.00%)	0
Cerebrovascular accident † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Presyncope † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Spinal cord compression † 1	0/327 (0.00%)	0	1/161 (0.62%)	2
Syncope † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Transient ischaemic attack † 1	1/327 (0.31%)	1	1/161 (0.62%)	1
Renal and urinary disorders
Acute kidney injury † 1	4/327 (1.22%)	5	0/161 (0.00%)	0
Chronic kidney disease † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Nephrolithiasis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Urinary tract obstruction † 1	1/327 (0.31%)	2	0/161 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	3/327 (0.92%)	5	1/161 (0.62%)	1
Pharyngeal inflammation † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Pleural effusion † 1	0/327 (0.00%)	0	1/161 (0.62%)	2
Pneumonitis † 1	3/327 (0.92%)	3	0/161 (0.00%)	0
Pulmonary fibrosis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Respiratory failure † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Vascular disorders
Embolism † 1	8/327 (2.45%)	10	1/161 (0.62%)	1
Haematoma † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Pelvic venous thrombosis † 1	1/327 (0.31%)	1	0/161 (0.00%)	0
Peripheral ischaemia † 1	1/327 (0.31%)	2	0/161 (0.00%)	0
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Abemaciclib + NSAI		Placebo + NSAI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	320/327 (97.86%)		135/161 (83.85%)
Blood and lymphatic system disorders
Anaemia † 1	93/327 (28.44%)	251	8/161 (4.97%)	15
Leukopenia † 1	68/327 (20.80%)	237	4/161 (2.48%)	6
Lymphopenia † 1	23/327 (7.03%)	51	4/161 (2.48%)	4
Neutropenia † 1	135/327 (41.28%)	507	3/161 (1.86%)	18
Thrombocytopenia † 1	34/327 (10.40%)	68	3/161 (1.86%)	10
Eye disorders
Lacrimation increased † 1	19/327 (5.81%)	26	1/161 (0.62%)	1
Gastrointestinal disorders
Abdominal pain † 1	95/327 (29.05%)	139	18/161 (11.18%)	21
Constipation † 1	51/327 (15.60%)	69	20/161 (12.42%)	24
Diarrhoea † 1	264/327 (80.73%)	922	48/161 (29.81%)	84
Dyspepsia † 1	25/327 (7.65%)	31	3/161 (1.86%)	3
Nausea † 1	126/327 (38.53%)	220	32/161 (19.88%)	41
Stomatitis † 1	37/327 (11.31%)	47	17/161 (10.56%)	23
Vomiting † 1	92/327 (28.13%)	131	18/161 (11.18%)	30
General disorders
Fatigue † 1	131/327 (40.06%)	240	51/161 (31.68%)	74
Influenza like illness † 1	34/327 (10.40%)	46	13/161 (8.07%)	16
Oedema peripheral † 1	30/327 (9.17%)	36	9/161 (5.59%)	9
Pain † 1	26/327 (7.95%)	32	9/161 (5.59%)	10
Pyrexia † 1	24/327 (7.34%)	29	12/161 (7.45%)	13
Infections and infestations
Upper respiratory tract infection † 1	31/327 (9.48%)	37	8/161 (4.97%)	11
Urinary tract infection † 1	27/327 (8.26%)	35	15/161 (9.32%)	25
Investigations
Alanine aminotransferase increased † 1	51/327 (15.60%)	120	11/161 (6.83%)	14
Aspartate aminotransferase increased † 1	48/327 (14.68%)	98	12/161 (7.45%)	13
Blood creatinine increased † 1	61/327 (18.65%)	126	6/161 (3.73%)	7
Weight decreased † 1	33/327 (10.09%)	60	5/161 (3.11%)	8
Metabolism and nutrition disorders
Decreased appetite † 1	80/327 (24.46%)	122	15/161 (9.32%)	20
Hypokalaemia † 1	22/327 (6.73%)	38	1/161 (0.62%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	41/327 (12.54%)	64	27/161 (16.77%)	39
Back pain † 1	39/327 (11.93%)	49	24/161 (14.91%)	30
Bone pain † 1	25/327 (7.65%)	32	12/161 (7.45%)	14
Myalgia † 1	28/327 (8.56%)	32	9/161 (5.59%)	11
Pain in extremity † 1	25/327 (7.65%)	38	17/161 (10.56%)	21
Nervous system disorders
Dizziness † 1	37/327 (11.31%)	49	15/161 (9.32%)	17
Dysgeusia † 1	30/327 (9.17%)	36	3/161 (1.86%)	3
Headache † 1	51/327 (15.60%)	84	24/161 (14.91%)	35
Neuropathy † 1	30/327 (9.17%)	35	13/161 (8.07%)	15
Psychiatric disorders
Insomnia † 1	22/327 (6.73%)	25	14/161 (8.70%)	15
Respiratory, thoracic and mediastinal disorders
Cough † 1	43/327 (13.15%)	60	15/161 (9.32%)	22
Dyspnoea † 1	39/327 (11.93%)	52	8/161 (4.97%)	12
Skin and subcutaneous tissue disorders
Alopecia † 1	87/327 (26.61%)	91	17/161 (10.56%)	18
Dry skin † 1	27/327 (8.26%)	36	4/161 (2.48%)	4
Pruritus † 1	43/327 (13.15%)	61	14/161 (8.70%)	17
Rash † 1	47/327 (14.37%)	64	8/161 (4.97%)	12
Vascular disorders
Hot flush † 1	32/327 (9.79%)	33	27/161 (16.77%)	31
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979
• EMail: clinicaltrials.gov@lilly.com

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02246621 History of Changes
• Other Study ID Numbers: 15417; I3Y-MC-JPBM ( Other Identifier: Eli Lilly and Company ); 2014-001502-18 ( EudraCT Number )
• First Submitted: September 18, 2014
• First Posted: September 23, 2014
• Results First Submitted: January 31, 2018
• Results First Posted: March 23, 2018
• Last Update Posted: September 10, 2019