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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02246621
Collaborator
(none)
493
Enrollment
167
Locations
2
Arms
106.8
Anticipated Duration (Months)
3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate how effective nonsteroidal aromatase inhibitors (NSAI) plus abemaciclib are in postmenopausal women with breast cancer. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
493 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Nonsteroidal Aromatase Inhibitors (Anastrozole or Letrozole) Plus LY2835219, a CDK4/6 Inhibitor, or Placebo in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer With No Prior Systemic Therapy in This Disease Setting
Actual Study Start Date :
Nov 6, 2014
Actual Primary Completion Date :
Jan 31, 2017
Anticipated Study Completion Date :
Sep 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Abemaciclib + NSAI

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).

Drug: Abemaciclib
Administered orally
Other Names:
  • LY2835219

    • Drug: Anastrozole
    Administered orally

    Drug: Letrozole
    Administered orally
    Placebo Comparator: Placebo + NSAI

    Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).

    Drug: Anastrozole
    Administered orally

    Drug: Letrozole
    Administered orally

    Drug: Placebo
    Administered orally

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)]

      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.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Randomization to Progressive Disease or Death Due to Any Cause (Estimated Up to 82 Months)]

      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.

    2. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)]

      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.

    3. Duration of Response (DoR) [CR or PR to Disease Progression or Death Due to Any Cause (Up to 32 Months)]

      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.

    4. Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) [Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)]

      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.

    5. Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR]) [Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)]

      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.

    6. 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 [Baseline, End of Study (Up to 32 Months)]

      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 with higher score indicating better functioning. For functional domains and global health status, higher scores represent a better level of functioning. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.

    7. Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores [Baseline, End of Study (Up to 32 Months)]

      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 indicated greater symptom burden. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline. Small changes are generally defined as at least a 3, 4 or 5 point change from baseline.

    8. Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire [Baseline, End of Study (Up to 32 Months)]

      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. A higher score representing a higher ("better") level of functioning (BR23: body image, sexual functioning, future perspective), or a higher ("worse") level of symptoms. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.

    9. Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value [Baseline, End of Study (Up to 32 Months)]

      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. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.

    10. Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale [Baseline, End of Study (Up to 32 Months)]

      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. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.

    11. 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 [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]

      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

    12. PK: Hepatic Clearance of Abemaciclib, and Apparent Hepatic Clearance of Its Metabolites M2 and M20 [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]

      PK: Hepatic Clearance of Abemaciclib, and apparent hepatic clearance of its Metabolites M2 and M20

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have a diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer

    • Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease

    • Have postmenopausal status

    • Have either measurable disease or nonmeasurable bone-only disease

    • Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale

    • Have adequate organ function

    • Have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture prior to randomization and recovered from the acute effects of therapy

    • Are able to swallow capsules

    Exclusion Criteria:

    • Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis

    • Have inflammatory breast cancer

    • Have clinical evidence or a history of central nervous system (CNS) metastasis

    • Are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer

    • Have received prior (neo)adjuvant endocrine therapy with a disease-free interval ≤12 months from completion of treatment

    • Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer

    • Have received prior treatment with everolimus

    • Have received prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)

    • Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization

    • Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study

    • Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively

    • Have had major surgery within 14 days prior to randomization

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer & Research Centers Chandler Arizona United States 85224
    2 Arizona Oncology Associates, PC - CASA Tucson Arizona United States 85715
    3 Highlands Oncology Group Fayetteville Arkansas United States 72703
    4 Comprehensive Blood and Cancer Center Bakersfield California United States 93309
    5 California Cancer Associates Research and Excellence (cCARE) Fresno California United States 93720
    6 St. Joseph Heritage Medical Group Fullerton California United States 92835
    7 UCLA Medical Center Los Angeles California United States 90024
    8 TRIO - Translational Research in Oncology-US, Inc. Los Angeles California United States 90095
    9 North Valley Hematology/Oncology Medical Group Northridge California United States 91328
    10 Central Coast Medical Oncology Corporation Santa Monica California United States 93454
    11 Catholic Health Initiatives (CHI) Englewood Colorado United States 80112
    12 St Mary's Hospital Regional Cancer Center Grand Junction Colorado United States 81501
    13 Holy Cross Hospital Inc. Fort Lauderdale Florida United States 33308
    14 Lakeland Regional Cancer Center Lakeland Florida United States 33805
    15 Lakes Research LLC Miami Lakes Florida United States 33104
    16 Moroose, Reynolds and Castillo Orlando Florida United States 32804
    17 Georgia Regents University Augusta Georgia United States 30912
    18 Summit Cancer Care Savannah Georgia United States 31404
    19 Franciscan St. Francis Health Indianapolis Indiana United States 46237
    20 IU Health Ball Memorial Hospital Muncie Indiana United States 47303-3499
    21 Office: Dr Jayne S Gurtler Metairie Louisiana United States 70006-2921
    22 Walter Reed National Military Medical Center IRB Bethesda Maryland United States 20889
    23 Mayo Clinic Rochester Minnesota United States 55905-0002
    24 St. Francis Medical Center Grand Island Nebraska United States 68802
    25 Nebraska Hematology-Oncology Lincoln Nebraska United States 68506
    26 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    27 Broome Oncology Johnson City New York United States 13790
    28 Beth Israel Medical Center New York New York United States 10011
    29 Mid Ohio Oncology Hematology Columbus Ohio United States 43219
    30 Kaiser Permanente / Central Interstate Medical Office Portland Oregon United States 97227
    31 University of Tennessee Medical Center Knoxville Tennessee United States 37920
    32 Oncology Consultants Cancer Center Houston Texas United States 77030
    33 Joe Arrington Cancer Center Lubbock Texas United States 79410
    34 Scott & White Healthcare Round Rock Texas United States 78665
    35 Scott & White Memorial Hosptial & Clinic Temple Texas United States 76508
    36 Cancer Care Northwest Valley Washington United States 99216
    37 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Camperdown Australia 2050
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    40 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Murdoch Australia 6150
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    46 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Innsbruck Austria 6020
    47 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Linz Austria 4010
    48 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Wien Austria 1090
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    54 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Edmonton Alberta Canada T6G 1Z2
    55 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Oshawa Ontario Canada L1G 2B9
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    58 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Montreal Quebec Canada H3T 1E2
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    75 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Ulm Germany 89075
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    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT02246621
    Other Study ID Numbers:
    • 15417
    • I3Y-MC-JPBM
    • 2014-001502-18
    First Posted:
    Sep 23, 2014
    Last Update Posted:
    Jul 27, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Eli Lilly and Company
    MONARCH 3
    Additional relevant MeSH terms:
    Breast Neoplasms
    Letrozole
    Anastrozole

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Completers are participants who died.
    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 327 161
    COMPLETED 63 30
    NOT COMPLETED 265 135

    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 Participants 328 165 493
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63.13
    (9.92)
    62.92
    (9.96)
    63.05
    (9.92)
    Sex: Female, Male (Count of Participants)
    Female
    328
    100%
    165
    100%
    493
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    32
    9.8%
    12
    7.3%
    44
    8.9%
    Not Hispanic or Latino
    230
    70.1%
    125
    75.8%
    355
    72%
    Unknown or Not Reported
    66
    20.1%
    28
    17%
    94
    19.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    4
    1.2%
    3
    1.8%
    7
    1.4%
    Asian
    103
    31.4%
    45
    27.3%
    148
    30%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.6%
    1
    0.2%
    Black or African American
    5
    1.5%
    3
    1.8%
    8
    1.6%
    White
    186
    56.7%
    102
    61.8%
    288
    58.4%
    More than one race
    2
    0.6%
    0
    0%
    2
    0.4%
    Unknown or Not Reported
    28
    8.5%
    11
    6.7%
    39
    7.9%
    Region of Enrollment (Count of Participants)
    Australia
    9
    2.7%
    6
    3.6%
    15
    3%
    Austria
    10
    3%
    3
    1.8%
    13
    2.6%
    Belgium
    14
    4.3%
    7
    4.2%
    21
    4.3%
    Canada
    14
    4.3%
    11
    6.7%
    25
    5.1%
    Germany
    11
    3.4%
    5
    3%
    16
    3.2%
    Spain
    16
    4.9%
    14
    8.5%
    30
    6.1%
    France
    30
    9.1%
    11
    6.7%
    41
    8.3%
    United Kingdom
    7
    2.1%
    2
    1.2%
    9
    1.8%
    Greece
    0
    0%
    1
    0.6%
    1
    0.2%
    Israel
    28
    8.5%
    19
    11.5%
    47
    9.5%
    Italy
    11
    3.4%
    11
    6.7%
    22
    4.5%
    Japan
    38
    11.6%
    15
    9.1%
    53
    10.8%
    South Korea
    41
    12.5%
    18
    10.9%
    59
    12%
    Mexico
    22
    6.7%
    7
    4.2%
    29
    5.9%
    Netherlands
    2
    0.6%
    4
    2.4%
    6
    1.2%
    New Zealand
    1
    0.3%
    0
    0%
    1
    0.2%
    Russia
    13
    4%
    6
    3.6%
    19
    3.9%
    Slovakia
    2
    0.6%
    0
    0%
    2
    0.4%
    Sweden
    3
    0.9%
    1
    0.6%
    4
    0.8%
    Turkey
    9
    2.7%
    3
    1.8%
    12
    2.4%
    Taiwan
    23
    7%
    9
    5.5%
    32
    6.5%
    United States
    24
    7.3%
    12
    7.3%
    36
    7.3%

    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 32 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who had evaluable data. Censored participants: Abemaciclib + NSAI = 190 and Placebo + NSAI =57.
    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).
    Measure Participants 328 165
    Median (95% Confidence Interval) [Months]
    28.18
    14.76
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.000002
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.54
    Confidence Interval (2-Sided) 95%
    0.418 to 0.698
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    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 32 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).
    Measure Participants 328 165
    Number (95% Confidence Interval) [Percentage of Participants]
    49.7
    15.2%
    37
    22.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    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 32 Months)

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who had evaluable data. Censored participants: Abemaciclib + NSAI = 112 and Placebo + NSAI =28.
    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).
    Measure Participants 163 61
    Median (95% Confidence Interval) [Months]
    27.39
    17.46
    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 32 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).
    Measure Participants 328 165
    Number (95% Confidence Interval) [Percentage of Participants]
    88.7
    27%
    86.7
    52.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.501
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    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 32 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).
    Measure Participants 328 165
    Number (95% Confidence Interval) [Percentage of Participants]
    78.0
    23.8%
    71.5
    43.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.101
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    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 with higher score indicating better functioning. For functional domains and global health status, higher scores represent a better level of functioning. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.
    Time Frame Baseline, End of Study (Up to 32 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).
    Measure Participants 328 165
    Physical
    -1.0
    (0.9)
    1.7
    (1.2)
    Role
    -1.4
    (1.1)
    2.9
    (1.6)
    Emotional
    4.7
    (0.9)
    4.0
    (1.3)
    Cognitive
    -4.0
    (0.9)
    -4.0
    (1.3)
    Social
    -0.1
    (1.0)
    3.3
    (1.4)
    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 indicated greater symptom burden. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline. Small changes are generally defined as at least a 3, 4 or 5 point change from baseline.
    Time Frame Baseline, End of Study (Up to 32 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).
    Measure Participants 328 165
    Fatigue
    2.4
    (1.0)
    -2.6
    (1.4)
    Nausea and Vomiting
    2.4
    (0.6)
    -0.4
    (0.9)
    Pain
    -4.8
    (1.0)
    -5.7
    (1.5)
    Dyspnea
    0.9
    (1.0)
    -1.6
    (1.4)
    Insomnia
    -1.7
    (1.2)
    -4.1
    (1.7)
    Appetite loss
    0.2
    (1.1)
    -3.9
    (1.6)
    Constipation
    -0.8
    (0.9)
    1.6
    (1.3)
    Diarrhea
    18.2
    (1.0)
    -0.5
    (1.5)
    Financial difficulties
    -0.7
    (1.1)
    -1.2
    (1.6)
    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. A higher score representing a higher ("better") level of functioning (BR23: body image, sexual functioning, future perspective), or a higher ("worse") level of symptoms. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.
    Time Frame Baseline, End of Study (Up to 32 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).
    Measure Participants 328 165
    Body image
    -4.5
    (1.1)
    0.6
    (1.6)
    Sexual functioning
    -0.2
    (0.7)
    -0.1
    (1.0)
    Future perspective
    12.7
    (1.3)
    11.9
    (1.9)
    Systemic therapy side effects
    8.15
    (0.68)
    3.68
    (0.98)
    Breast symptoms
    -6.12
    (0.64)
    -6.23
    (0.93)
    Arm symptoms
    -1.14
    (0.87)
    -2.23
    (1.27)
    10. Secondary Outcome
    Title Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value
    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. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.
    Time Frame Baseline, End of Study (Up to 32 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).
    Measure Participants 328 165
    Least Squares Mean (Standard Error) [units on a scale]
    0.01
    (0.01)
    0.01
    (0.01)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.688
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.01
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.02
    Estimation Comments
    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. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.
    Time Frame Baseline, End of Study (Up to 32 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).
    Measure Participants 328 165
    Least Squares Mean (Standard Error) [millimeter (mm)]
    0.49
    (0.78)
    1.51
    (1.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Abemaciclib + NSAI, Placebo + NSAI
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.466
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.01
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.39
    Estimation Comments
    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 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
    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).
    Measure Participants 322
    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 PK: Hepatic Clearance of Abemaciclib, and apparent hepatic clearance of its Metabolites M2 and M20
    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).
    Measure Participants 322
    Abemaciclib
    23.0
    (26.7)
    M2
    21.6
    (50.4)
    M20
    26.0
    (46.4)

    Adverse Events

    Time Frame Baseline Up to 32 Months
    Adverse Event Reporting Description Serious Adverse Events and Other Adverse Events: All participants who received at least one dose of study drug; All-Cause Mortality: All randomized participants.
    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 (%) # Events Affected / at Risk (%) # Events
    Total 63/328 (19.2%) 30/165 (18.2%)
    Serious Adverse Events
    Abemaciclib + NSAI Placebo + NSAI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 102/327 (31.2%) 27/161 (16.8%)
    Blood and lymphatic system disorders
    Anaemia 6/327 (1.8%) 6 0/161 (0%) 0
    Disseminated intravascular coagulation 1/327 (0.3%) 1 0/161 (0%) 0
    Neutropenia 2/327 (0.6%) 2 0/161 (0%) 0
    Cardiac disorders
    Acute coronary syndrome 0/327 (0%) 0 1/161 (0.6%) 1
    Angina pectoris 1/327 (0.3%) 1 0/161 (0%) 0
    Atrial fibrillation 2/327 (0.6%) 3 0/161 (0%) 0
    Atrial tachycardia 1/327 (0.3%) 2 0/161 (0%) 0
    Cardiac failure 2/327 (0.6%) 2 0/161 (0%) 0
    Myocardial infarction 0/327 (0%) 0 1/161 (0.6%) 1
    Pericardial effusion 1/327 (0.3%) 1 0/161 (0%) 0
    Stress cardiomyopathy 0/327 (0%) 0 1/161 (0.6%) 1
    Supraventricular tachycardia 2/327 (0.6%) 2 0/161 (0%) 0
    Ventricular arrhythmia 1/327 (0.3%) 1 0/161 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/327 (0%) 0 1/161 (0.6%) 1
    Vertigo positional 1/327 (0.3%) 1 0/161 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/327 (0.3%) 1 2/161 (1.2%) 2
    Colitis 1/327 (0.3%) 2 0/161 (0%) 0
    Constipation 1/327 (0.3%) 1 0/161 (0%) 0
    Diarrhoea 5/327 (1.5%) 7 0/161 (0%) 0
    Enterocolitis 2/327 (0.6%) 2 0/161 (0%) 0
    Food poisoning 1/327 (0.3%) 1 0/161 (0%) 0
    Gastritis 1/327 (0.3%) 1 0/161 (0%) 0
    Ileus 1/327 (0.3%) 1 1/161 (0.6%) 1
    Intestinal obstruction 1/327 (0.3%) 1 0/161 (0%) 0
    Nausea 1/327 (0.3%) 2 0/161 (0%) 0
    Oesophagitis 1/327 (0.3%) 1 0/161 (0%) 0
    Pancreatitis 1/327 (0.3%) 1 0/161 (0%) 0
    Periodontal disease 1/327 (0.3%) 1 0/161 (0%) 0
    Rectal haemorrhage 1/327 (0.3%) 1 1/161 (0.6%) 1
    Vomiting 2/327 (0.6%) 3 2/161 (1.2%) 2
    General disorders
    General physical health deterioration 2/327 (0.6%) 2 1/161 (0.6%) 2
    Inflammation 1/327 (0.3%) 1 0/161 (0%) 0
    Non-cardiac chest pain 0/327 (0%) 0 1/161 (0.6%) 1
    Pyrexia 1/327 (0.3%) 1 1/161 (0.6%) 1
    Sudden death 0/327 (0%) 0 1/161 (0.6%) 1
    Ulcer haemorrhage 1/327 (0.3%) 1 0/161 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 1/327 (0.3%) 1 0/161 (0%) 0
    Cholecystitis 2/327 (0.6%) 2 1/161 (0.6%) 1
    Hepatitis toxic 1/327 (0.3%) 2 0/161 (0%) 0
    Immune system disorders
    Anaphylactic reaction 1/327 (0.3%) 1 1/161 (0.6%) 1
    Infections and infestations
    Appendicitis 1/327 (0.3%) 1 0/161 (0%) 0
    Bacteraemia 1/327 (0.3%) 1 0/161 (0%) 0
    Cellulitis 2/327 (0.6%) 2 0/161 (0%) 0
    Diverticulitis 1/327 (0.3%) 1 0/161 (0%) 0
    Erysipelas 1/327 (0.3%) 1 0/161 (0%) 0
    Gastroenteritis 0/327 (0%) 0 1/161 (0.6%) 1
    Kidney infection 2/327 (0.6%) 2 0/161 (0%) 0
    Lung infection 13/327 (4%) 17 0/161 (0%) 0
    Mastitis 1/327 (0.3%) 1 0/161 (0%) 0
    Sepsis 2/327 (0.6%) 2 1/161 (0.6%) 1
    Skin infection 1/327 (0.3%) 2 1/161 (0.6%) 1
    Urinary tract infection 4/327 (1.2%) 4 1/161 (0.6%) 1
    Wound infection 0/327 (0%) 0 1/161 (0.6%) 1
    Injury, poisoning and procedural complications
    Ankle fracture 1/327 (0.3%) 1 0/161 (0%) 0
    Fall 2/327 (0.6%) 3 1/161 (0.6%) 1
    Fracture 3/327 (0.9%) 3 1/161 (0.6%) 1
    Hip fracture 3/327 (0.9%) 3 0/161 (0%) 0
    Spinal fracture 1/327 (0.3%) 1 0/161 (0%) 0
    Wound dehiscence 1/327 (0.3%) 1 0/161 (0%) 0
    Wrist fracture 0/327 (0%) 0 1/161 (0.6%) 1
    Investigations
    Alanine aminotransferase increased 1/327 (0.3%) 1 0/161 (0%) 0
    Aspartate aminotransferase increased 1/327 (0.3%) 1 0/161 (0%) 0
    Blood bilirubin increased 1/327 (0.3%) 1 0/161 (0%) 0
    Blood creatinine increased 3/327 (0.9%) 3 0/161 (0%) 0
    Ejection fraction decreased 0/327 (0%) 0 1/161 (0.6%) 1
    Gamma-glutamyltransferase increased 0/327 (0%) 0 1/161 (0.6%) 1
    Metabolism and nutrition disorders
    Cachexia 0/327 (0%) 0 1/161 (0.6%) 1
    Decreased appetite 1/327 (0.3%) 1 1/161 (0.6%) 1
    Dehydration 4/327 (1.2%) 5 2/161 (1.2%) 2
    Hypercalcaemia 1/327 (0.3%) 1 0/161 (0%) 0
    Hyperkalaemia 2/327 (0.6%) 2 0/161 (0%) 0
    Hypokalaemia 1/327 (0.3%) 1 0/161 (0%) 0
    Hyponatraemia 3/327 (0.9%) 4 0/161 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/327 (0.3%) 1 0/161 (0%) 0
    Arthritis 2/327 (0.6%) 2 0/161 (0%) 0
    Back pain 1/327 (0.3%) 1 0/161 (0%) 0
    Bone pain 1/327 (0.3%) 1 0/161 (0%) 0
    Muscular weakness 0/327 (0%) 0 1/161 (0.6%) 2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/327 (0.3%) 1 0/161 (0%) 0
    Breast cancer metastatic 0/327 (0%) 0 1/161 (0.6%) 1
    Endometrial cancer 1/327 (0.3%) 1 0/161 (0%) 0
    Tumour haemorrhage 0/327 (0%) 0 1/161 (0.6%) 1
    Nervous system disorders
    Cerebral ischaemia 1/327 (0.3%) 2 0/161 (0%) 0
    Cerebrovascular accident 3/327 (0.9%) 3 1/161 (0.6%) 1
    Headache 1/327 (0.3%) 1 0/161 (0%) 0
    Presyncope 1/327 (0.3%) 1 0/161 (0%) 0
    Spinal cord compression 0/327 (0%) 0 1/161 (0.6%) 2
    Syncope 1/327 (0.3%) 1 0/161 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 5/327 (1.5%) 6 0/161 (0%) 0
    Chronic kidney disease 1/327 (0.3%) 1 0/161 (0%) 0
    Nephrolithiasis 1/327 (0.3%) 1 0/161 (0%) 0
    Urinary tract obstruction 1/327 (0.3%) 2 0/161 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 3/327 (0.9%) 5 0/161 (0%) 0
    Pharyngeal inflammation 1/327 (0.3%) 1 0/161 (0%) 0
    Pleural effusion 0/327 (0%) 0 1/161 (0.6%) 2
    Pneumonitis 4/327 (1.2%) 5 0/161 (0%) 0
    Pulmonary fibrosis 1/327 (0.3%) 1 0/161 (0%) 0
    Respiratory failure 2/327 (0.6%) 3 0/161 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 1/327 (0.3%) 1 0/161 (0%) 0
    Skin ulcer 0/327 (0%) 0 1/161 (0.6%) 1
    Vascular disorders
    Embolism 8/327 (2.4%) 10 1/161 (0.6%) 1
    Haematoma 1/327 (0.3%) 1 0/161 (0%) 0
    Hypertension 1/327 (0.3%) 1 0/161 (0%) 0
    Pelvic venous thrombosis 1/327 (0.3%) 1 0/161 (0%) 0
    Peripheral ischaemia 1/327 (0.3%) 2 0/161 (0%) 0
    Other (Not Including Serious) Adverse Events
    Abemaciclib + NSAI Placebo + NSAI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 322/327 (98.5%) 141/161 (87.6%)
    Blood and lymphatic system disorders
    Anaemia 102/327 (31.2%) 328 13/161 (8.1%) 21
    Leukopenia 72/327 (22%) 293 4/161 (2.5%) 6
    Lymphopenia 24/327 (7.3%) 67 6/161 (3.7%) 6
    Neutropenia 143/327 (43.7%) 625 3/161 (1.9%) 20
    Thrombocytopenia 41/327 (12.5%) 91 5/161 (3.1%) 12
    Eye disorders
    Dry eye 17/327 (5.2%) 19 1/161 (0.6%) 1
    Lacrimation increased 23/327 (7%) 30 1/161 (0.6%) 1
    Gastrointestinal disorders
    Abdominal pain 102/327 (31.2%) 158 20/161 (12.4%) 24
    Constipation 57/327 (17.4%) 81 23/161 (14.3%) 29
    Diarrhoea 267/327 (81.7%) 984 52/161 (32.3%) 97
    Dyspepsia 26/327 (8%) 33 5/161 (3.1%) 5
    Nausea 135/327 (41.3%) 239 33/161 (20.5%) 44
    Stomatitis 41/327 (12.5%) 55 17/161 (10.6%) 25
    Vomiting 98/327 (30%) 146 20/161 (12.4%) 31
    General disorders
    Fatigue 135/327 (41.3%) 255 54/161 (33.5%) 79
    Influenza like illness 39/327 (11.9%) 54 15/161 (9.3%) 19
    Oedema peripheral 33/327 (10.1%) 41 10/161 (6.2%) 11
    Pain 27/327 (8.3%) 35 11/161 (6.8%) 14
    Pyrexia 33/327 (10.1%) 40 16/161 (9.9%) 19
    Infections and infestations
    Upper respiratory tract infection 33/327 (10.1%) 48 9/161 (5.6%) 15
    Urinary tract infection 34/327 (10.4%) 46 16/161 (9.9%) 31
    Injury, poisoning and procedural complications
    Fall 17/327 (5.2%) 24 3/161 (1.9%) 3
    Investigations
    Alanine aminotransferase increased 57/327 (17.4%) 143 12/161 (7.5%) 17
    Aspartate aminotransferase increased 55/327 (16.8%) 119 12/161 (7.5%) 14
    Blood alkaline phosphatase increased 19/327 (5.8%) 25 6/161 (3.7%) 7
    Blood creatinine increased 67/327 (20.5%) 174 7/161 (4.3%) 8
    Weight decreased 36/327 (11%) 65 5/161 (3.1%) 8
    Metabolism and nutrition disorders
    Decreased appetite 86/327 (26.3%) 140 17/161 (10.6%) 23
    Hypokalaemia 28/327 (8.6%) 48 2/161 (1.2%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 56/327 (17.1%) 91 33/161 (20.5%) 50
    Back pain 52/327 (15.9%) 67 26/161 (16.1%) 33
    Bone pain 33/327 (10.1%) 42 14/161 (8.7%) 20
    Muscular weakness 17/327 (5.2%) 27 6/161 (3.7%) 10
    Myalgia 34/327 (10.4%) 38 12/161 (7.5%) 15
    Pain in extremity 35/327 (10.7%) 50 19/161 (11.8%) 26
    Nervous system disorders
    Dizziness 44/327 (13.5%) 57 18/161 (11.2%) 20
    Dysgeusia 31/327 (9.5%) 37 5/161 (3.1%) 5
    Headache 64/327 (19.6%) 102 26/161 (16.1%) 37
    Neuropathy 35/327 (10.7%) 42 16/161 (9.9%) 17
    Psychiatric disorders
    Anxiety 11/327 (3.4%) 16 9/161 (5.6%) 11
    Insomnia 24/327 (7.3%) 28 16/161 (9.9%) 17
    Reproductive system and breast disorders
    Breast pain 14/327 (4.3%) 20 10/161 (6.2%) 13
    Respiratory, thoracic and mediastinal disorders
    Cough 48/327 (14.7%) 69 20/161 (12.4%) 27
    Dyspnoea 40/327 (12.2%) 56 11/161 (6.8%) 15
    Skin and subcutaneous tissue disorders
    Alopecia 90/327 (27.5%) 95 18/161 (11.2%) 19
    Dry skin 31/327 (9.5%) 39 4/161 (2.5%) 4
    Nail ridging 17/327 (5.2%) 20 2/161 (1.2%) 2
    Pruritus 47/327 (14.4%) 68 15/161 (9.3%) 19
    Rash 50/327 (15.3%) 72 8/161 (5%) 14
    Vascular disorders
    Hot flush 33/327 (10.1%) 34 28/161 (17.4%) 35
    Hypertension 24/327 (7.3%) 46 10/161 (6.2%) 24

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    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
    Other Study ID Numbers:
    • 15417
    • I3Y-MC-JPBM
    • 2014-001502-18
    First Posted:
    Sep 23, 2014
    Last Update Posted:
    Jul 27, 2022
    Last Verified:
    Jul 1, 2022