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A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (MONARCH 2)

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ClinicalTrials.gov Identifier: NCT02107703
Recruitment Status : Recruiting
First Posted : April 8, 2014
Results First Posted : March 13, 2018
Last Update Posted : February 22, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Neoplasms
Interventions Drug: Abemaciclib
Drug: Fulvestrant
Drug: Placebo
Enrollment 669
Recruitment Details  
Pre-assignment Details In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description 150 milligrams (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 supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Period Title: Overall Study
Started 446 223
Received at Least 1 Dose of Study Drug 441 223
Completed 85 48
Not Completed 361 175
Reason Not Completed
Withdrawal by Subject             36             19
Lost to Follow-up             6             4
On study treatment/follow up             319             152
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant Total
Hide Arm/Group Description 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 supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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. Total of all reporting groups
Overall Number of Baseline Participants 446 223 669
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 446 participants 223 participants 669 participants
59.3  (11.2) 61.1  (11.7) 59.9  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 446 participants 223 participants 669 participants
Female 446 223 669
Male 0 0 0
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 443 participants 223 participants 666 participants
Hispanic or Latino 57 25 82
Not Hispanic or Latino 303 162 465
Unknown or Not Reported 83 36 119
[1]
Measure Analysis Population Description: All randomized participants who had baseline Ethnicity data.
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 446 participants 223 participants 669 participants
American Indian or Alaska Native 18 8 26
Asian 149 65 214
Native Hawaiian or Other Pacific Islander 0 0 0
Black or African American 9 5 14
White 237 136 373
More than one race 0 0 0
Unknown or Not Reported 33 9 42
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
North America Number Analyzed 446 participants 223 participants 669 participants
120 58 178
Europe Number Analyzed 446 participants 223 participants 669 participants
179 100 279
Taiwan Number Analyzed 446 participants 223 participants 669 participants
25 14 39
Japan Number Analyzed 446 participants 223 participants 669 participants
64 31 95
South Korea Number Analyzed 446 participants 223 participants 669 participants
58 20 78
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
Time Frame From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Censored participants: Abemaciclib=224.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
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 supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 446 223
Median (95% Confidence Interval)
Unit of Measure: Months
16.4
(14.4 to 19.3)
9.3
(7.4 to 11.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Abemaciclib + Fulvestrant, Placebo + Fulvestrant
Comments The final analysis was planned at 378 PFS events, which would provide approximately 90% power assuming a hazard ratio (HR) of 0.703 at a one-sided α of 0.025.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0000001
Comments This is two sided P value and it is statistically significant.
Method Log Rank
Comments Log rank test is stratified by endocrine sensitivity and natural of disease by interactive web response system (IWRS).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.553
Confidence Interval (2-Sided) 95%
0.449 to 0.681
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame From Date of Randomization until Death Due to Any Cause (Up To 80 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants. Censored participants: Abemaciclib=361.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
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 supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 446 223
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(26.7 to NA)
NA [1] 
(26.8 to NA)
[1]
The upper limit of the 95% CI was not calculated due to the high censoring rate.
3.Secondary Outcome
Title Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Hide 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. 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.
Time Frame From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
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 supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 446 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
35.2
(30.8 to 39.6)
16.1
(11.3 to 21.0)
4.Secondary Outcome
Title Duration of Response (DOR)
Hide 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. 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.
Time Frame From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with response.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 157 36
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(18.05 to NA)
25.6
(11.9 to 25.6)
[1]
The median DoR for participants has not been reached.
5.Secondary Outcome
Title Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])
Hide Description 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.
Time Frame From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 446 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
83.0
(79.5 to 86.4)
75.8
(70.2 to 81.4)
6.Secondary Outcome
Title Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])
Hide Description 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.
Time Frame From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 446 223
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
72.2
(68.0 to 76.4)
56.1
(49.5 to 62.6)
7.Secondary Outcome
Title Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)
Hide Description 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.
Time Frame Baseline, End of Study (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug with a baseline and at least 1 post-baseline result.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 441 223
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.06  (0.07) 0.00  (0.10)
8.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20
Hide Description Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of 150 mg study drug (Abemaciclib) with evaluable Abemaciclib, M2 and M20 PK data.
Arm/Group Title Abemaciclib + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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.
Overall Number of Participants Analyzed 326
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms*hour/milliliters (ng*h/mL)
Abemaciclib
2960
(32.2%)
M2
1640
(70.2%)
M20
2870
(69.6%)
9.Secondary Outcome
Title Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)
Hide Description 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.
Time Frame Baseline, End of Study (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 441 223
Least Squares Mean (Standard Error)
Unit of Measure: mm
0.12  (0.65) 1.16  (0.92)
10.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline, Short Term Follow Up (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 180 126
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Global health status Number Analyzed 179 participants 126 participants
-4.57  (1.55) -8.15  (1.87)
Functional scale: Physical functioning Number Analyzed 179 participants 126 participants
-3.76  (1.29) -7.59  (1.59)
Functional scale: Role functioning Number Analyzed 179 participants 124 participants
-4.87  (1.73) -9.58  (2.12)
Functional scale: Emotional functioning Number Analyzed 179 participants 125 participants
2.38  (1.38) -2.44  (1.70)
Functional scale: Cognitive functioning Number Analyzed 180 participants 125 participants
-3.16  (1.29) -2.96  (1.58)
Functional scale: Social functioning Number Analyzed 180 participants 126 participants
-4.62  (1.61) -4.78  (1.97)
Symptom scale: Fatigue Number Analyzed 180 participants 125 participants
5.01  (1.45) 7.83  (1.78)
Symptom scale: Nausea and vomiting Number Analyzed 180 participants 125 participants
2.81  (1.35) 6.49  (1.64)
Symptom scale: Pain Number Analyzed 180 participants 126 participants
-0.47  (1.82) 4.38  (2.21)
Symptom scale: Dyspnoea Number Analyzed 180 participants 123 participants
5.21  (1.70) 5.39  (2.10)
Symptom scale: Insomnia Number Analyzed 180 participants 126 participants
-0.04  (1.86) 3.76  (2.27)
Symptom scale: Appetite loss Number Analyzed 180 participants 125 participants
2.06  (1.85) 6.40  (2.23)
Symptom scale: Constipation Number Analyzed 179 participants 125 participants
-0.15  (1.59) 3.79  (1.92)
Symptom scale: Diarrhoea Number Analyzed 179 participants 125 participants
4.14  (1.66) 2.67  (1.99)
Symptom scale: Financial difficulties Number Analyzed 179 participants 124 participants
0.34  (1.60) 2.85  (1.96)
11.Secondary Outcome
Title Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire
Hide Description 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.
Time Frame Baseline, Short Term Follow Up (Up To 31 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
Overall Number of Participants Analyzed 182 126
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Functional scale: Body image Number Analyzed 179 participants 125 participants
-2.20  (1.46) -3.27  (1.83)
Functional scale:Sexual functioning Number Analyzed 171 participants 116 participants
0.41  (1.00) -1.60  (1.25)
Functional scale: Future perspective Number Analyzed 179 participants 126 participants
6.06  (2.06) 10.05  (2.51)
Symptom scale: Systemic therapy side effects Number Analyzed 182 participants 125 participants
7.23  (1.00) 6.98  (1.22)
Symptom scale: Breast symptoms Number Analyzed 181 participants 126 participants
-2.10  (0.89) -0.96  (1.09)
Symptom scale: Arm symptoms Number Analyzed 182 participants 125 participants
-0.45  (1.29) 0.10  (1.59)
Time Frame Up To 31 Months
Adverse Event Reporting Description All randomized participants who received at least one dose of study drug.
 
Arm/Group Title Abemaciclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description 150 milligrams (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 will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections 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.
All-Cause Mortality
Abemaciclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) Affected / at Risk (%)
Total   9/441 (2.04%)      2/223 (0.90%)    
Show Serious Adverse Events Hide Serious Adverse Events
Abemaciclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   99/441 (22.45%)      24/223 (10.76%)    
Blood and lymphatic system disorders     
Anaemia  1  4/441 (0.91%)  4 0/223 (0.00%)  0
Disseminated intravascular coagulation  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Febrile neutropenia  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Neutropenia  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Cardiac disorders     
Atrial fibrillation  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Atrioventricular block first degree  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Cardiac arrest  1  0/441 (0.00%)  0 1/223 (0.45%)  2
Cardiac failure  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Myocardial infarction  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Sinus tachycardia  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Supraventricular tachycardia  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Ventricular tachycardia  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Gastrointestinal disorders     
Abdominal pain  1  5/441 (1.13%)  5 1/223 (0.45%)  1
Ascites  1  1/441 (0.23%)  1 1/223 (0.45%)  2
Diarrhoea  1  7/441 (1.59%)  7 0/223 (0.00%)  0
Enterocolitis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Gastritis  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Intestinal obstruction  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Nausea  1  5/441 (1.13%)  5 1/223 (0.45%)  1
Oesophageal pain  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Volvulus  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Vomiting  1  2/441 (0.45%)  2 0/223 (0.00%)  0
General disorders     
Malaise  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Multiple organ dysfunction syndrome  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Non-cardiac chest pain  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Oedema peripheral  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Pyrexia  1  3/441 (0.68%)  4 0/223 (0.00%)  0
Surgical failure  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Hepatobiliary disorders     
Cholangitis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Cholecystitis  1  3/441 (0.68%)  3 0/223 (0.00%)  0
Drug-induced liver injury  1  2/441 (0.45%)  4 0/223 (0.00%)  0
Hepatic failure  1  2/441 (0.45%)  3 0/223 (0.00%)  0
Hepatic function abnormal  1  2/441 (0.45%)  4 0/223 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Sarcoidosis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Infections and infestations     
Bartholin's abscess  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Cellulitis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Enterocolitis infectious  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Gastroenteritis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Kidney infection  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Lower respiratory tract infection  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Lung infection  1  7/441 (1.59%)  8 0/223 (0.00%)  0
Mastitis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Osteomyelitis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Pyelonephritis acute  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Salmonella bacteraemia  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Sepsis  1  6/441 (1.36%)  9 1/223 (0.45%)  1
Skin infection  1  3/441 (0.68%)  3 1/223 (0.45%)  1
Soft tissue infection  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Upper respiratory tract infection  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Urinary tract infection  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Injury, poisoning and procedural complications     
Ankle fracture  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Fall  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Fracture  1  3/441 (0.68%)  3 1/223 (0.45%)  1
Hip fracture  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Limb injury  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Wound complication  1  3/441 (0.68%)  3 0/223 (0.00%)  0
Wrist fracture  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Aspartate aminotransferase increased  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Blood alkaline phosphatase increased  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Blood bilirubin increased  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Blood creatinine increased  1  3/441 (0.68%)  3 0/223 (0.00%)  0
Blood follicle stimulating hormone abnormal  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Electrocardiogram qt prolonged  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Hormone level abnormal  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Oestradiol abnormal  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  1/441 (0.23%)  1 1/223 (0.45%)  2
Dehydration  1  3/441 (0.68%)  3 1/223 (0.45%)  1
Hyperglycaemia  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Hypocalcaemia  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Hypokalaemia  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  2/441 (0.45%)  2 2/223 (0.90%)  2
Bone pain  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Muscular weakness  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Musculoskeletal chest pain  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Musculoskeletal pain  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Myositis  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign bone neoplasm  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Colon cancer  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Tumour pain  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Nervous system disorders     
Cerebrovascular accident  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Depressed level of consciousness  1  1/441 (0.23%)  2 1/223 (0.45%)  1
Dizziness  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Headache  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Neuropathy  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Syncope  1  1/441 (0.23%)  1 1/223 (0.45%)  1
Psychiatric disorders     
Confusional state  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  2/441 (0.45%)  2 0/223 (0.00%)  0
Chronic kidney disease  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Urinary retention  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Reproductive system and breast disorders     
Pelvic pain  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  0/441 (0.00%)  0 1/223 (0.45%)  1
Chronic obstructive pulmonary disease  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Dyspnoea  1  6/441 (1.36%)  7 2/223 (0.90%)  3
Pleural effusion  1  2/441 (0.45%)  2 5/223 (2.24%)  5
Pneumonitis  1  4/441 (0.91%)  5 0/223 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Surgical and medical procedures     
Bartholin's cyst removal  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Cholecystectomy  1  1/441 (0.23%)  1 0/223 (0.00%)  0
Vascular disorders     
Embolism  1  9/441 (2.04%)  10 1/223 (0.45%)  1
Lymphoedema  1  0/441 (0.00%)  0 1/223 (0.45%)  1
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Abemaciclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   432/441 (97.96%)      187/223 (83.86%)    
Blood and lymphatic system disorders     
Anaemia  1  127/441 (28.80%)  342 8/223 (3.59%)  11
Leukopenia  1  125/441 (28.34%)  501 4/223 (1.79%)  9
Lymphopenia  1  32/441 (7.26%)  91 1/223 (0.45%)  7
Neutropenia  1  203/441 (46.03%)  808 8/223 (3.59%)  14
Thrombocytopenia  1  69/441 (15.65%)  154 6/223 (2.69%)  7
Eye disorders     
Lacrimation increased  1  29/441 (6.58%)  33 3/223 (1.35%)  3
Gastrointestinal disorders     
Abdominal pain  1  152/441 (34.47%)  267 34/223 (15.25%)  53
Constipation  1  60/441 (13.61%)  74 30/223 (13.45%)  41
Diarrhoea  1  380/441 (86.17%)  1182 55/223 (24.66%)  85
Dry mouth  1  30/441 (6.80%)  32 14/223 (6.28%)  14
Dyspepsia  1  27/441 (6.12%)  30 10/223 (4.48%)  11
Nausea  1  198/441 (44.90%)  351 50/223 (22.42%)  69
Stomatitis  1  67/441 (15.19%)  95 23/223 (10.31%)  27
Vomiting  1  114/441 (25.85%)  193 23/223 (10.31%)  38
General disorders     
Chills  1  25/441 (5.67%)  29 1/223 (0.45%)  1
Fatigue  1  176/441 (39.91%)  288 60/223 (26.91%)  79
Influenza like illness  1  33/441 (7.48%)  50 15/223 (6.73%)  18
Injection site reaction  1  36/441 (8.16%)  47 22/223 (9.87%)  40
Oedema peripheral  1  50/441 (11.34%)  61 15/223 (6.73%)  16
Pain  1  23/441 (5.22%)  29 8/223 (3.59%)  9
Pyrexia  1  46/441 (10.43%)  69 13/223 (5.83%)  14
Infections and infestations     
Upper respiratory tract infection  1  49/441 (11.11%)  58 17/223 (7.62%)  24
Urinary tract infection  1  38/441 (8.62%)  52 6/223 (2.69%)  6
Investigations     
Alanine aminotransferase increased  1  58/441 (13.15%)  108 12/223 (5.38%)  26
Aspartate aminotransferase increased  1  54/441 (12.24%)  93 15/223 (6.73%)  28
Blood creatinine increased  1  51/441 (11.56%)  109 1/223 (0.45%)  1
Weight decreased  1  46/441 (10.43%)  76 5/223 (2.24%)  8
Metabolism and nutrition disorders     
Decreased appetite  1  116/441 (26.30%)  166 26/223 (11.66%)  28
Hypokalaemia  1  29/441 (6.58%)  62 5/223 (2.24%)  6
Musculoskeletal and connective tissue disorders     
Arthralgia  1  51/441 (11.56%)  92 32/223 (14.35%)  49
Back pain  1  41/441 (9.30%)  55 26/223 (11.66%)  33
Bone pain  1  21/441 (4.76%)  24 15/223 (6.73%)  19
Muscular weakness  1  46/441 (10.43%)  83 13/223 (5.83%)  17
Myalgia  1  33/441 (7.48%)  40 13/223 (5.83%)  16
Pain in extremity  1  35/441 (7.94%)  73 7/223 (3.14%)  9
Nervous system disorders     
Dizziness  1  54/441 (12.24%)  81 13/223 (5.83%)  15
Dysgeusia  1  79/441 (17.91%)  105 6/223 (2.69%)  7
Headache  1  88/441 (19.95%)  147 34/223 (15.25%)  65
Neuropathy  1  32/441 (7.26%)  38 21/223 (9.42%)  25
Psychiatric disorders     
Depression  1  23/441 (5.22%)  25 8/223 (3.59%)  11
Insomnia  1  31/441 (7.03%)  36 17/223 (7.62%)  20
Respiratory, thoracic and mediastinal disorders     
Cough  1  59/441 (13.38%)  69 25/223 (11.21%)  28
Dyspnoea  1  45/441 (10.20%)  53 23/223 (10.31%)  26
Oropharyngeal pain  1  21/441 (4.76%)  22 12/223 (5.38%)  13
Skin and subcutaneous tissue disorders     
Alopecia  1  69/441 (15.65%)  82 4/223 (1.79%)  4
Dry skin  1  38/441 (8.62%)  43 3/223 (1.35%)  6
Pruritus  1  57/441 (12.93%)  70 13/223 (5.83%)  14
Rash  1  48/441 (10.88%)  70 10/223 (4.48%)  13
Vascular disorders     
Hot flush  1  46/441 (10.43%)  67 22/223 (9.87%)  25
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
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
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02107703     History of Changes
Other Study ID Numbers: 15362
I3Y-MC-JPBL ( Other Identifier: Eli Lilly and Company )
2013-004728-13 ( EudraCT Number )
First Submitted: April 4, 2014
First Posted: April 8, 2014
Results First Submitted: February 12, 2018
Results First Posted: March 13, 2018
Last Update Posted: February 22, 2019