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

Phase 3Active Not RecruitingNCT02246621

Eli Lilly and Company493 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

493

Conditions

Breast Cancer

Interventions

AbemaciclibDRUG

Administered orally

AnastrozoleDRUG

Administered orally

LetrozoleDRUG

Administered orally

Placebo

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (155)

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

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)

Secondary Outcomes

Overall Survival (OS)

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)

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

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)

Data from ClinicalTrials.gov

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Ironwood Cancer & Research Centers

Chandler, Arizona, United States

Highlands Oncology Group

Springdale, Arkansas, United States

CBCC Global Research, Inc.

Bakersfield, California, United States

California Cancer Associates Research and Excellence

Fresno, California, United States

TRIO-US (Translational Research in Oncology-US)

Los Angeles, California, United States

Central Coast Medical Oncology Corporation

Los Angeles, California, United States

Orlando Health, Inc

Los Angeles, California, United States

North Valley Hematology/Oncology Medical Group

Los Angeles, California, United States

UCLA Hematology/Oncology - Parkside

Santa Monica, California, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

...and 145 more locations

Duration of Response (DoR)

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)

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

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)

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

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)

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

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.