Breast Cancer, Early-Stage Breast Carcinoma, Hormone Receptor Positive Tumor
Conditions
Keywords
cyclin-dependent kinase (CDK) 4/6 inhibitor, CDK 4 and 6 inhibitor
Brief summary
The purpose of this study is to evaluate the biological effects of abemaciclib in combination with anastrozole and compare those to the effects of abemaciclib alone and anastrozole alone in the tumors of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer.
Interventions
DRUGAbemaciclib
Administered orally
DRUGLoperamide
Administered orally
DRUGAnastrozole
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have postmenopausal status. * Adenocarcinoma of the breast. * Breast tumor ≥1 centimeter (cm) in diameter, HR+, HER2-. * Neoadjuvant endocrine monotherapy is deemed to be a suitable therapy. * Primary breast cancer that is suitable for baseline core biopsy. * Have adequate organ function.
Exclusion criteria
* Bilateral invasive breast cancer. * Metastatic breast cancer (local spread to axillary lymph nodes is permitted). * Inflammatory breast cancer. * Prior systemic therapy or radiotherapy for invasive or non-invasive breast cancer in the same breast as currently being treated. * Prior radiotherapy to the ipsilateral chest wall for any malignancy. * Prior anti-estrogen therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to 2 Weeks in Ki67 Expression | Baseline, 2 Weeks | Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR) or Partial Response (PR): Clinical Objective Response | From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) | Clinical objective response is defined as the percentage of participants with the best overall response rate (ORR) with a best OR of CR or PR, according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1. ORR is recorded from the start of the study treatment until the earliest of objective progression or start of new anticancer therapy. A responder depends on target and non-target disease and the appearance of new lesions. CR is defined as the disappearance of all non-target lesions. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. All lymph nodes are non-pathological or normal in size (\<10mm short axis). Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, a relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm. |
| Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response | From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) | Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions. |
| Percentage of Participants With Pathologic Complete Response (pCR) | From Start of Treatment Up to 16 Weeks | pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes. |
| Pharmacokinetics (PK): Apparent Clearance of Abemaciclib | Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose | Abemaciclib apparent clearance (CL/F) was calculated by population nonlinear mixed effects modeling (NONMEM) using all available data spanning cycles 1 and cycles 3-5. |
| PK: Apparent Volume of Distribution of Abemaciclib | Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose | Abemaciclib apparent volume of distribution was calculated by population NONMEM using all available data spanning cycles 1 and cycles 3-5. |
| Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline, 2 Weeks | EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. |
Countries
Austria, Belgium, Canada, Germany, Italy, Netherlands, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Participants who had progressive disease at the end of the study but off study drug were considered to have completed the study. Participants were randomized to anastrozole, or abemaciclib, and abemaciclib + anastrozole in cycle 1. All participants received abemaciclib + anastrozole post cycle 1.
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib + Anastrozole Participants were given 150 mg of abemaciclib orally Q12H plus 1 mg of anastrozole orally QD for 2 weeks.
All participants received 150 mg of abemaciclib orally Q12H plus 1 mg of anastrozole orally QD for an additional 14 weeks.
Total treatment duration was 16 weeks. | 74 |
| Abemaciclib Participants received 150 mg of abemaciclib orally Q12H for 2 weeks.
All participants received 150 mg of abemaciclib orally Q12H plus 1 mg of anastrozole QD for an additional 14 weeks.
Total treatment duration was 16 weeks. | 76 |
| Anastrozole Participants received 1 mg of anastrozole orally QD for 2 weeks.
All participants received 150 mg of abemaciclib orally Q12H plus 1 mg of anastrozole orally QD for an additional 14 weeks.
Total treatment duration was 16 weeks. | 74 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Cycle 1 Period 1 (2 Weeks) | Adverse Event | 1 | 1 | 0 |
| Cycle 1 Period 1 (2 Weeks) | Never Treated | 0 | 1 | 0 |
| Cycle 1 Period 1 (2 Weeks) | Physician Decision | 1 | 0 | 0 |
| Cycle 1 Period 1 (2 Weeks) | Withdrawal by Subject | 0 | 3 | 0 |
| Cycle 2-5 Period 2 (14 Weeks) | Adverse Event | 15 | 0 | 0 |
| Cycle 2-5 Period 2 (14 Weeks) | Noncompliance with study drug | 1 | 0 | 0 |
| Cycle 2-5 Period 2 (14 Weeks) | Physician Decision | 1 | 0 | 0 |
| Cycle 2-5 Period 2 (14 Weeks) | Protocol Deviation | 1 | 0 | 0 |
| Cycle 2-5 Period 2 (14 Weeks) | Withdrawal by Subject | 9 | 0 | 0 |
| Extension Period (8 Weeks) | Adverse Event | 1 | 0 | 0 |
| Extension Period (8 Weeks) | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Abemaciclib + Anastrozole | Abemaciclib | Anastrozole | Total |
|---|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.4 | 63.8 years STANDARD_DEVIATION 7.9 | 64.9 years STANDARD_DEVIATION 8.4 | 64.2 years STANDARD_DEVIATION 8.2 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully Active) | 69 Participants | 70 Participants | 63 Participants | 202 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted, able to do light sedentary work) | 5 Participants | 5 Participants | 10 Participants | 20 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Unreported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 8 Participants | 5 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 61 Participants | 60 Participants | 182 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | 9 Participants | 23 Participants |
| Ki67 at Baseline | 27.24 Percent Cells Positive STANDARD_DEVIATION 13.56 | 27.88 Percent Cells Positive STANDARD_DEVIATION 12.13 | 26.86 Percent Cells Positive STANDARD_DEVIATION 12.32 | 27.33 Percent Cells Positive STANDARD_DEVIATION 12.63 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 16 Participants | 16 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 55 Participants | 57 Participants | 55 Participants | 167 Participants |
| Region of Enrollment Austria | 10 Participants | 4 Participants | 12 Participants | 26 Participants |
| Region of Enrollment Belgium | 5 Participants | 2 Participants | 4 Participants | 11 Participants |
| Region of Enrollment Canada | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Germany | 5 Participants | 6 Participants | 4 Participants | 15 Participants |
| Region of Enrollment Italy | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Region of Enrollment Netherlands | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Region of Enrollment South Korea | 5 Participants | 7 Participants | 2 Participants | 14 Participants |
| Region of Enrollment Spain | 13 Participants | 16 Participants | 8 Participants | 37 Participants |
| Region of Enrollment Taiwan | 5 Participants | 7 Participants | 11 Participants | 23 Participants |
| Region of Enrollment United States | 26 Participants | 28 Participants | 26 Participants | 80 Participants |
| Sex: Female, Male Female | 74 Participants | 76 Participants | 74 Participants | 224 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 74 | 58 / 75 | 17 / 74 | 189 / 217 |
| serious Total, serious adverse events | 1 / 74 | 1 / 75 | 0 / 74 | 16 / 217 |
Outcome results
Primary
Percent Change From Baseline to 2 Weeks in Ki67 Expression
Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay.
Time frame: Baseline, 2 Weeks
Population: All randomized participants who received at least one dose of study drug and a valid baseline Ki67 measurement of at least 5% and a valid 2-week measurement of any magnitude.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Abemaciclib + Anastrozole | Percent Change From Baseline to 2 Weeks in Ki67 Expression | -92.86 Percent Change |
| Abemaciclib | Percent Change From Baseline to 2 Weeks in Ki67 Expression | -90.52 Percent Change |
| Anastrozole | Percent Change From Baseline to 2 Weeks in Ki67 Expression | -62.78 Percent Change |
p-value: <0.00190% CI: [0.13, 0.28]t-test, 1 sided
p-value: <0.00190% CI: [0.17, 0.38]t-test, 1 sided
Secondary
Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.
Time frame: Baseline, 2 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable data for EORTC QLQ.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Social Functioning | -8.3 units on a scale | Standard Deviation 18.8 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Role Functioning | -11.3 units on a scale | Standard Deviation 23.7 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Insomnia | -1.1 units on a scale | Standard Deviation 19.1 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Fatigue | 13.6 units on a scale | Standard Deviation 23.2 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Physical Functioning | -3.2 units on a scale | Standard Deviation 10.2 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Dyspnea | 1.1 units on a scale | Standard Deviation 19.1 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Nausea/Vomiting | 11.8 units on a scale | Standard Deviation 17.7 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Constipation | 22.4 units on a scale | Standard Deviation 31.5 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Pain | 4.8 units on a scale | Standard Deviation 19.9 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Emotional | 5.4 units on a scale | Standard Deviation 17.1 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Financial Impact | -2.8 units on a scale | Standard Deviation 19.7 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Global Health Status | -9.5 units on a scale | Standard Deviation 17.9 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Cognitive | 0.5 units on a scale | Standard Deviation 12.4 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Diarrhea | 18.3 units on a scale | Standard Deviation 29.4 |
| Abemaciclib + Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Appetite Loss | 16.9 units on a scale | Standard Deviation 28.3 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Appetite Loss | 16.9 units on a scale | Standard Deviation 27.5 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Global Health Status | -7.6 units on a scale | Standard Deviation 18.1 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Physical Functioning | -5.5 units on a scale | Standard Deviation 12.6 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Role Functioning | -11.4 units on a scale | Standard Deviation 24 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Emotional | 3.5 units on a scale | Standard Deviation 21.4 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Cognitive | -2.0 units on a scale | Standard Deviation 15.6 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Social Functioning | -3.5 units on a scale | Standard Deviation 16.7 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Fatigue | 13.9 units on a scale | Standard Deviation 22.6 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Nausea/Vomiting | 9.6 units on a scale | Standard Deviation 12.4 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Pain | 3.5 units on a scale | Standard Deviation 19.3 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Dyspnea | 0.5 units on a scale | Standard Deviation 19.8 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Insomnia | 0.5 units on a scale | Standard Deviation 29.5 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Constipation | 16.9 units on a scale | Standard Deviation 31.2 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Diarrhea | 27.8 units on a scale | Standard Deviation 25.9 |
| Abemaciclib | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Financial Impact | 2.0 units on a scale | Standard Deviation 18.4 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Social Functioning | -0.7 units on a scale | Standard Deviation 12.6 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Diarrhea | 0.0 units on a scale | Standard Deviation 15.1 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Insomnia | -1.9 units on a scale | Standard Deviation 22.1 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Cognitive | -1.4 units on a scale | Standard Deviation 11 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Emotional | 1.3 units on a scale | Standard Deviation 14 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Appetite Loss | 1.9 units on a scale | Standard Deviation 15 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Role Functioning | -2.2 units on a scale | Standard Deviation 17.4 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Global Health Status | -2.3 units on a scale | Standard Deviation 13.4 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Constipation | 1.9 units on a scale | Standard Deviation 15 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Nausea/Vomiting | 2.7 units on a scale | Standard Deviation 7.4 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Physical Functioning | -0.3 units on a scale | Standard Deviation 7.5 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Pain | 2.9 units on a scale | Standard Deviation 16.7 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Fatigue | 4.0 units on a scale | Standard Deviation 12.8 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Financial Impact | 0.0 units on a scale | Standard Deviation 11.4 |
| Anastrozole | Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Dyspnea | -1.0 units on a scale | Standard Deviation 12.7 |
Secondary
Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response
Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions.
Time frame: From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks)
Population: All participants who received combination treatment post cycle 1. Radiological/surgery assessments occurred at the start of treatment and at the end of the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib + Anastrozole | Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response | 46.4 percentage of participants |
Secondary
Percentage of Participants With Complete Response (CR) or Partial Response (PR): Clinical Objective Response
Clinical objective response is defined as the percentage of participants with the best overall response rate (ORR) with a best OR of CR or PR, according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1. ORR is recorded from the start of the study treatment until the earliest of objective progression or start of new anticancer therapy. A responder depends on target and non-target disease and the appearance of new lesions. CR is defined as the disappearance of all non-target lesions. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. All lymph nodes are non-pathological or normal in size (\<10mm short axis). Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, a relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm.
Time frame: From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks)
Population: All participants who received combination treatment post cycle 1. Radiological/surgery assessments occurred at the start of treatment and at the end of the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib + Anastrozole | Percentage of Participants With Complete Response (CR) or Partial Response (PR): Clinical Objective Response | 53.6 percentage of participants |
Secondary
Percentage of Participants With Pathologic Complete Response (pCR)
pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes.
Time frame: From Start of Treatment Up to 16 Weeks
Population: All participants who received combination treatment post cycle 1 and had evaluable pCR data. Radiological/surgery assessments occurred at the start of treatment and at the end of the treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib + Anastrozole | Percentage of Participants With Pathologic Complete Response (pCR) | 3.7 percentage of participants |
Secondary
Pharmacokinetics (PK): Apparent Clearance of Abemaciclib
Abemaciclib apparent clearance (CL/F) was calculated by population nonlinear mixed effects modeling (NONMEM) using all available data spanning cycles 1 and cycles 3-5.
Time frame: Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose
Population: All randomized participants who received at least one dose of abemaciclib across cycles 1 and cycles 3-5. The results are summarized by the original randomized arms of cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib + Anastrozole | Pharmacokinetics (PK): Apparent Clearance of Abemaciclib | 24.0 Liters/hour (L/h) | Geometric Coefficient of Variation 32 |
| Abemaciclib | Pharmacokinetics (PK): Apparent Clearance of Abemaciclib | 19.1 Liters/hour (L/h) | Geometric Coefficient of Variation 55 |
| Anastrozole | Pharmacokinetics (PK): Apparent Clearance of Abemaciclib | 24.4 Liters/hour (L/h) | Geometric Coefficient of Variation 61 |
Secondary
PK: Apparent Volume of Distribution of Abemaciclib
Abemaciclib apparent volume of distribution was calculated by population NONMEM using all available data spanning cycles 1 and cycles 3-5.
Time frame: Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose
Population: All randomized participants who received at least one dose of abemaciclib across cycles 1 and cycles 3-5. The results are summarized by the original randomized arms of cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib + Anastrozole | PK: Apparent Volume of Distribution of Abemaciclib | 941 Liters (L) | Geometric Coefficient of Variation 53 |
| Abemaciclib | PK: Apparent Volume of Distribution of Abemaciclib | 720 Liters (L) | Geometric Coefficient of Variation 58 |
| Anastrozole | PK: Apparent Volume of Distribution of Abemaciclib | 758 Liters (L) | Geometric Coefficient of Variation 49 |