Breast Cancer
Conditions
Keywords
early stage breast cancer, cyclin-dependent kinase (CDK)
Brief summary
The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.
Interventions
DRUGAbemaciclib
Administered orally.
Administered according to label instructions.
Sponsors
Eli Lilly and Company
NSABP Foundation Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations). * The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases. * The participant must have undergone definitive surgery of the primary breast tumor. * The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. * Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence: * 4 or more positive axillary lymph nodes * Tumor size of at least 5 centimeters * Grade 3 defined as at least 8 points on the Bloom Richardson grading system * Ki-67 index by central analysis of ≥20% on untreated breast tissue * The participant must be randomized within 16 months from the time of definitive breast cancer surgery. * The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last. * Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery. * Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods. * The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1. * The participant has adequate organ function. * The participant is able to swallow oral medications.
Exclusion criteria
* Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease. * Participants with inflammatory breast cancer. * Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded. * Females who are pregnant or lactating. * The participant has previously received treatment with any CDK4 and CDK6 inhibitor. * The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate). * The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene. * The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. * The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE). * The participant has active systemic infections or viral load. * The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Disease Free Survival (IDFS) | Baseline to Recurrence or Death from Any Cause (Up to 32 Months) | IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IDFS for Participants With Ki-67 Index ≥20% | Baseline to Recurrence or Death from Any Cause (Approximately 10 Years) | Outcome data will be provided after the study is completed. |
| Distant Relapse-Free Survival (DRFS) | Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months) | Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first. |
| Overall Survival (OS) | Baseline to Death from Any Cause (Approximately 10 Years) | Outcome data will be provided after the study is completed. |
| Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib | Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose | Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib |
| Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) | Baseline, Follow Up (Approximately 3 Years) | Outcome data will be provided after the study is completed. |
| Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) | Baseline, Follow Up (Approximately 3 Years)] | Outcome data will be provided after the study is completed. |
| Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | Baseline, Follow Up (Approximately 3 Years)] | Outcome data will be provided after the study is completed. |
| Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) | Baseline, Follow Up (Approximately 3 Years)] | Outcome data will be provided after the study is completed. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORCall 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
Participant flow
Recruitment details
Completers included participants who had recurrence disease, death due to any cause, and participants off treatment but on study follow-up.
Participants by arm
| Arm | Count |
|---|---|
| 150 mg Abemaciclib + Endocrine Therapy Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met. | 2,808 |
| Endocrine Therapy Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met. | 2,829 |
| Total | 5,637 |
Baseline characteristics
| Characteristic | 150 mg Abemaciclib + Endocrine Therapy | Endocrine Therapy | Total |
|---|---|---|---|
| Age, Continuous | 52.20 years STANDARD_DEVIATION 11.26 | 52.10 years STANDARD_DEVIATION 11.2 | 52.10 years STANDARD_DEVIATION 11.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 355 Participants | 378 Participants | 733 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1734 Participants | 1738 Participants | 3472 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 719 Participants | 713 Participants | 1432 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 64 Participants | 58 Participants | 122 Participants |
| Race (NIH/OMB) Asian | 675 Participants | 669 Participants | 1344 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 53 Participants | 110 Participants |
| Race (NIH/OMB) More than one race | 22 Participants | 25 Participants | 47 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 40 Participants | 42 Participants | 82 Participants |
| Race (NIH/OMB) White | 1947 Participants | 1978 Participants | 3925 Participants |
| Region of Enrollment Argentina | 77 Participants | 68 Participants | 145 Participants |
| Region of Enrollment Australia | 108 Participants | 109 Participants | 217 Participants |
| Region of Enrollment Austria | 22 Participants | 20 Participants | 42 Participants |
| Region of Enrollment Belgium | 65 Participants | 51 Participants | 116 Participants |
| Region of Enrollment Brazil | 144 Participants | 153 Participants | 297 Participants |
| Region of Enrollment Canada | 28 Participants | 16 Participants | 44 Participants |
| Region of Enrollment China | 187 Participants | 170 Participants | 357 Participants |
| Region of Enrollment Czechia | 15 Participants | 12 Participants | 27 Participants |
| Region of Enrollment Denmark | 54 Participants | 58 Participants | 112 Participants |
| Region of Enrollment Finland | 45 Participants | 49 Participants | 94 Participants |
| Region of Enrollment France | 86 Participants | 101 Participants | 187 Participants |
| Region of Enrollment Germany | 148 Participants | 152 Participants | 300 Participants |
| Region of Enrollment Greece | 74 Participants | 64 Participants | 138 Participants |
| Region of Enrollment Hong Kong | 8 Participants | 12 Participants | 20 Participants |
| Region of Enrollment Hungary | 24 Participants | 28 Participants | 52 Participants |
| Region of Enrollment India | 59 Participants | 53 Participants | 112 Participants |
| Region of Enrollment Israel | 39 Participants | 38 Participants | 77 Participants |
| Region of Enrollment Italy | 72 Participants | 59 Participants | 131 Participants |
| Region of Enrollment Japan | 181 Participants | 196 Participants | 377 Participants |
| Region of Enrollment Mexico | 104 Participants | 121 Participants | 225 Participants |
| Region of Enrollment Netherlands | 5 Participants | 14 Participants | 19 Participants |
| Region of Enrollment New Zealand | 21 Participants | 22 Participants | 43 Participants |
| Region of Enrollment Poland | 65 Participants | 60 Participants | 125 Participants |
| Region of Enrollment Portugal | 21 Participants | 16 Participants | 37 Participants |
| Region of Enrollment Puerto Rico | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment Romania | 53 Participants | 60 Participants | 113 Participants |
| Region of Enrollment Russia | 66 Participants | 73 Participants | 139 Participants |
| Region of Enrollment Saudi Arabia | 5 Participants | 9 Participants | 14 Participants |
| Region of Enrollment Singapore | 11 Participants | 21 Participants | 32 Participants |
| Region of Enrollment South Africa | 3 Participants | 6 Participants | 9 Participants |
| Region of Enrollment South Korea | 122 Participants | 123 Participants | 245 Participants |
| Region of Enrollment Spain | 144 Participants | 148 Participants | 292 Participants |
| Region of Enrollment Sweden | 7 Participants | 5 Participants | 12 Participants |
| Region of Enrollment Taiwan | 64 Participants | 60 Participants | 124 Participants |
| Region of Enrollment Turkey | 125 Participants | 110 Participants | 235 Participants |
| Region of Enrollment Ukraine | 54 Participants | 51 Participants | 105 Participants |
| Region of Enrollment United Kingdom | 99 Participants | 100 Participants | 199 Participants |
| Region of Enrollment United States | 402 Participants | 418 Participants | 820 Participants |
| Sex: Female, Male Female | 2787 Participants | 2814 Participants | 5601 Participants |
| Sex: Female, Male Male | 21 Participants | 15 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 38 / 2,791 | 36 / 2,800 |
| other Total, other adverse events | 2,723 / 2,791 | 2,318 / 2,800 |
| serious Total, serious adverse events | 344 / 2,791 | 202 / 2,800 |
Outcome results
Primary
Invasive Disease Free Survival (IDFS)
IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause.
Time frame: Baseline to Recurrence or Death from Any Cause (Up to 32 Months)
Population: All randomized participants (including the censored participants). 2672 participants were censored in 150 mg Abemaciclib + Endocrine Therapy, 2642 participants were censored in Endocrine Therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Abemaciclib + Endocrine Therapy | Invasive Disease Free Survival (IDFS) | NA Months |
| Endocrine Therapy | Invasive Disease Free Survival (IDFS) | NA Months |
p-value: 0.0095795% CI: [0.598, 0.932]Log Rank
Secondary
Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
Outcome data will be provided after the study is completed.
Time frame: Baseline, Follow Up (Approximately 3 Years)]
Secondary
Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B)
Outcome data will be provided after the study is completed.
Time frame: Baseline, Follow Up (Approximately 3 Years)
Secondary
Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)
Outcome data will be provided after the study is completed.
Time frame: Baseline, Follow Up (Approximately 3 Years)]
Secondary
Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Outcome data will be provided after the study is completed.
Time frame: Baseline, Follow Up (Approximately 3 Years)]
Secondary
Distant Relapse-Free Survival (DRFS)
Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first.
Time frame: Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)
Population: All randomized participants (including the censored participants). 2702 participants were censored in 150 mg Abemaciclib + Endocrine Therapy, 2677 participants were censored in Endocrine Therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 150 mg Abemaciclib + Endocrine Therapy | Distant Relapse-Free Survival (DRFS) | NA Months |
| Endocrine Therapy | Distant Relapse-Free Survival (DRFS) | NA Months |
95% CI: [0.559, 0.92]
Secondary
IDFS for Participants With Ki-67 Index ≥20%
Outcome data will be provided after the study is completed.
Time frame: Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)
Secondary
Overall Survival (OS)
Outcome data will be provided after the study is completed.
Time frame: Baseline to Death from Any Cause (Approximately 10 Years)
Secondary
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
Time frame: Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose
Population: All randomized participants who received at least one dose of Abemaciclib and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 150 mg Abemaciclib + Endocrine Therapy | Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib | 143 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 110 |