NCT02246621 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-02-03

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · POSTED

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

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outcome · POSTED

Duration of Response (DoR)

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outcome · POSTED

Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])

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outcome · POSTED

Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR])

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outcome · POSTED

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

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outcome · POSTED

Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores

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outcome · POSTED

Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire

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outcome · POSTED

Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value

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outcome · POSTED

Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale

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outcome · POSTED

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

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outcome · POSTED

PK: Hepatic Clearance of Abemaciclib, and Apparent Hepatic Clearance of Its Metabolites M2 and M20

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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).
intervention Names
Drug: Abemaciclib
Drug: Anastrozole
Drug: Letrozole
label
Abemaciclib + NSAI
type
EXPERIMENTAL
description
Placebo orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
intervention Names
Drug: Anastrozole
Drug: Letrozole
Drug: Placebo
label
Placebo + NSAI
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Abemaciclib + NSAI
description
Administered orally
name
Abemaciclib
other Names
LY2835219
type
DRUG
arm Group Labels
Abemaciclib + NSAI
Placebo + NSAI
description
Administered orally
name
Anastrozole
type
DRUG
arm Group Labels
Abemaciclib + NSAI
Placebo + NSAI
description
Administered orally
name
Letrozole
type
DRUG
arm Group Labels
Placebo + NSAI
description
Administered orally
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
CARE_PROVIDER

primary Purpose

TREATMENT

Enrollment

count: 493
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
Progression Free Survival (PFS)
time Frame
Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)

secondary Outcomes

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.
measure
Overall Survival (OS)
time Frame
Randomization to Progressive Disease or Death Due to Any Cause (Estimated Up to 82 Months)
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.
measure
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
time Frame
Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
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.
measure
Duration of Response (DoR)
time Frame
CR or PR to Disease Progression or Death Due to Any Cause (Up to 32 Months)
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.
measure
Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])
time Frame
Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
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.
measure
Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR])
time Frame
Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
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.
measure
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
time Frame
Baseline, End of Study (Up to 32 Months)
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.
measure
Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores
time Frame
Baseline, End of Study (Up to 32 Months)
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.
measure
Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire
time Frame
Baseline, End of Study (Up to 32 Months)
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.
measure
Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value
time Frame
Baseline, End of Study (Up to 32 Months)
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.
measure
Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale
time Frame
Baseline, End of Study (Up to 32 Months)
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
measure
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
description
PK: Hepatic Clearance of Abemaciclib, and apparent hepatic clearance of its Metabolites M2 and M20
measure
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

Full 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.

Source references

references

citation
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pmid
28968163
type
RESULT
citation
Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, Frenzel M, Hardebeck MC, Cox J, Barriga S, Toi M, Iwata H, Goetz MP. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019 Jan 17;5:5. doi: 10.1038/s41523-018-0097-z. eCollection 2019.
pmid
30675515
type
RESULT
citation
Hong J, Chen T, Ouyang L, Du N, Li A, Zhou Z, Zhang H, Xia Z, Meng J. Cost-effectiveness comparison of dalpiciclib and abemaciclib combined with an aromatase inhibitor as first-line treatment for HR+/HER2- advanced breast cancer. Expert Rev Pharmacoecon Outcomes Res. 2024 Apr;24(4):559-566. doi: 10.1080/14737167.2024.2330542. Epub 2024 Mar 20.
pmid
38470447
type
DERIVED
citation
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pmid
36861085
type
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citation
Takahashi M, Tokunaga E, Mori J, Tanizawa Y, van der Walt JS, Kawaguchi T, Goetz MP, Toi M. Japanese subgroup analysis of the phase 3 MONARCH 3 study of abemaciclib as initial therapy for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Breast Cancer. 2022 Jan;29(1):174-184. doi: 10.1007/s12282-021-01295-0. Epub 2021 Oct 18.
pmid
34661821
type
DERIVED
citation
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pmid
33392835
type
DERIVED