Breast Neoplasm, Neoplasm Metastasis
Conditions
Brief summary
This study will evaluate the effect of adding abemaciclib to fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer that progressed or recurred after previous treatment with a type of drug known as a CDK4/6 inhibitor and endocrine therapy. Participation could last up to 5 years, depending on how you and your tumor respond.
Interventions
DRUGAbemaciclib
Administered orally.
DRUGFulvestrant
Administered IM.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of HR+, HER2- locally advanced or metastatic breast cancer * Have radiologic evidence of disease progression or recurrence either * On treatment with a CDK4/6 inhibitor with aromatase inhibitor (AI) as initial therapy for advanced disease, or * On/after treatment with a CDK4/6 inhibitor plus endocrine therapy (ET) administered as adjuvant therapy for early stage breast cancer * Must be deemed appropriate for treatment with ET * If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression * Have Response Evaluable Criteria in Solid Tumors (RECIST) evaluable disease (measurable disease and/or nonmeasurable disease) * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982) * Have adequate renal, hematologic, and hepatic organ function * Must be able to swallow capsules/tablets
Exclusion criteria
* Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis * Have symptomatic or untreated central nervous system metastasis * Have received any systemic therapy between disease recurrence/progression and study screening * Have received more than 1 line of therapy for advanced or metastatic disease. * Have received prior chemotherapy for metastatic breast cancer (MBC) * Have received prior treatment with fulvestrant, any investigational estrogen receptor (ER)-directed therapy (including selective ER degraders \[SERDs\] and non-SERDs), any phosphatidylinositol 3-kinase (PI3K)-, mammalian target of rapamycin (mTOR)-, or protein kinase B (AKT)-inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Randomization to the date of first documented progression of disease or death from any cause (Up to 21 Months) | PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Determined by Blinded Independent Central Review (BICR) | Randomization to the date of first documented progression of disease or death from any cause (Up to 22 Months) | PFS is defined as the time from the date of randomization to the earliest date of disease progression determined by blinded independent central review (BICR) or death from any cause, whichever occurs first. |
| Objective Response Rate (ORR): Percentage of Participants Who Achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) | Randomization until measured progressive disease (Up to 22 Months) | ORR is the best overall tumor response of CR or PR as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. |
Countries
Argentina, Belgium, Czechia, Denmark, France, Greece, Hungary, Israel, Italy, Mexico, Poland, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), 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
Pre-assignment details
Completers included participants who had an event (progressive disease or death) and participants who were off the treatment and were alive at study conclusion.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Abemaciclib Plus Fulvestrant Abemaciclib 150 mg administered orally BID on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were met. | 182 |
| Arm B: Placebo Plus Fulvestrant Placebo administered orally BID on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500 mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation criteria were met. | 186 |
| Total | 368 |
Baseline characteristics
| Characteristic | Arm B: Placebo Plus Fulvestrant | Total | Arm A: Abemaciclib Plus Fulvestrant |
|---|---|---|---|
| Age, Continuous | 59.60 years STANDARD_DEVIATION 12.16 | 58.80 years STANDARD_DEVIATION 12.17 | 58.00 years STANDARD_DEVIATION 12.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 55 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 143 Participants | 278 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants | 35 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 26 Participants | 47 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 24 Participants | 12 Participants |
| Race (NIH/OMB) White | 143 Participants | 283 Participants | 140 Participants |
| Region of Enrollment Argentina | 20 Participants | 39 Participants | 19 Participants |
| Region of Enrollment Belgium | 5 Participants | 12 Participants | 7 Participants |
| Region of Enrollment Czechia | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Denmark | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment France | 10 Participants | 21 Participants | 11 Participants |
| Region of Enrollment Greece | 4 Participants | 12 Participants | 8 Participants |
| Region of Enrollment Hungary | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment Israel | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment Italy | 11 Participants | 27 Participants | 16 Participants |
| Region of Enrollment Mexico | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment Poland | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment South Korea | 10 Participants | 20 Participants | 10 Participants |
| Region of Enrollment Spain | 31 Participants | 58 Participants | 27 Participants |
| Region of Enrollment Taiwan | 14 Participants | 25 Participants | 11 Participants |
| Region of Enrollment Turkey | 25 Participants | 42 Participants | 17 Participants |
| Region of Enrollment United States | 28 Participants | 56 Participants | 28 Participants |
| Sex: Female, Male Female | 185 Participants | 365 Participants | 180 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 181 | 37 / 185 |
| other Total, other adverse events | 173 / 181 | 131 / 185 |
| serious Total, serious adverse events | 44 / 181 | 20 / 185 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (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 the date of first documented progression of disease or death from any cause (Up to 21 Months)
Population: All randomized participants (including censored). Censored participants: Abemaciclib plus fulvestrant (n = 65), Placebo plus fulvestrant (n = 45).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Abemaciclib Plus Fulvestrant | Progression-Free Survival (PFS) | 6 Months |
| Arm B: Placebo Plus Fulvestrant | Progression-Free Survival (PFS) | 5.3 Months |
p-value: 0.0295% CI: [0.57, 0.95]Log Rank
Secondary
Objective Response Rate (ORR): Percentage of Participants Who Achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)
ORR is the best overall tumor response of CR or PR as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time frame: Randomization until measured progressive disease (Up to 22 Months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Abemaciclib Plus Fulvestrant | Objective Response Rate (ORR): Percentage of Participants Who Achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) | 24 Percentage of participants |
| Arm B: Placebo Plus Fulvestrant | Objective Response Rate (ORR): Percentage of Participants Who Achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) | 10 Percentage of participants |
Secondary
Progression Free Survival (PFS) Determined by Blinded Independent Central Review (BICR)
PFS is defined as the time from the date of randomization to the earliest date of disease progression determined by blinded independent central review (BICR) or death from any cause, whichever occurs first.
Time frame: Randomization to the date of first documented progression of disease or death from any cause (Up to 22 Months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Abemaciclib Plus Fulvestrant | Progression Free Survival (PFS) Determined by Blinded Independent Central Review (BICR) | 12.9 Months |
| Arm B: Placebo Plus Fulvestrant | Progression Free Survival (PFS) Determined by Blinded Independent Central Review (BICR) | 5.6 Months |