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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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