Metastatic Breast Cancer
Conditions
Keywords
Endocrine Therapy, Taxane, MONARCH 1
Brief summary
The main purpose of this study is to evaluate whether the study drug known as abemaciclib is effective in treating participants with breast cancer who have already tried other drug treatments.
Interventions
DRUGAbemaciclib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. * Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer. * Recurrent, locally advanced, unresectable or metastatic breast cancer with disease progression following anti-estrogen therapy. * Prior treatment with at least 2 chemotherapy regimens: * At least 1 of these regimens must have been administered in the metastatic setting. * At least 1 of these regimens must have contained a taxane. * No more than 2 prior chemotherapy regimens in the metastatic setting. * Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale. * Have discontinued all previous therapies for cancer. * Have the presence of measureable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.1.
Exclusion criteria
* Have either a history of central nervous system (CNS) metastasis or evidence of CNS metastasis on the magnetic resonance image of brain obtained at baseline. * Received prior therapy with another cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. * Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug. * Have had major surgery within 14 days of the initial dose of study drug. * Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 14 Months) | 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. |
| Progression Free Survival (PFS) | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 27 Months) | 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 first dose, 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. |
| Percentage of Participants With CR, PR or SD (Disease Control Rate [DCR]) | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (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. |
| Overall Survival (OS) | From Date of First Dose until Death Due to Any Cause (Up To 27 Months) | 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. |
| Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | Cycle 6 Day 1 | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | Cycle 1 Day 1 pre dose, Cycle 1 Day 15 4 hours (h) and 7 h post dose, Cycle 2 Day 1 pre dose and 3 h post dose, Cycle 3 Day1 pre dose | Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) was evaluated for Abemaciclib and Metabolites M2 and M20 |
| Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | Cycle 6 Day 1 | EORTC QLQ-C30 v3.0 was 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. 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. |
| Percentage of Participants With Tumor Response of Stable Disease (SD) for at Least 6 Months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) | From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months) | Clinical benefit rate defined as percentage of patients 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. |
Countries
Belgium, France, Spain, United States
Participant flow
Pre-assignment details
In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib 200 mg abemaciclib given orally once every 12 hours for 28 days (1 cycle). Participants may continue to receive treatment until discontinuation criteria are met. | 132 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Abemaciclib |
|---|---|
| Age, Continuous | 59.13 Years STANDARD_DEVIATION 10.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) White | 112 Participants |
| Region of Enrollment Belgium | 28 Participants |
| Region of Enrollment France | 11 Participants |
| Region of Enrollment Spain | 23 Participants |
| Region of Enrollment United States | 70 Participants |
| Sex: Female, Male Female | 132 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 132 / 132 |
| serious Total, serious adverse events | 33 / 132 |
Outcome results
Primary
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: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib | Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) | 19.7 Percentage of participants |
Secondary
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: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Duration of Response (DOR) | 8.6 Months |
Secondary
Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score
A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Cycle 6 Day 1
Population: All randomized participants with a baseline and at least 1 post-baseline mBPI-sf data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abemaciclib | Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | Worse | 20 Participants |
| Abemaciclib | Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | Better | 18 Participants |
| Abemaciclib | Number of Participants With Categorical Change From Baseline in Brief Pain Inventory Short Form (mBPI-sf) - Worst Pain Score | No Change | 21 Participants |
Secondary
Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score
EORTC QLQ-C30 v3.0 was 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. 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: Cycle 6 Day 1
Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abemaciclib | Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | No Change | 16 Participants |
| Abemaciclib | Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | Worse | 26 Participants |
| Abemaciclib | Number of Participants With Categorical Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status Score | Better | 17 Participants |
Secondary
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: From Date of First Dose until Death Due to Any Cause (Up To 27 Months)
Population: All enrolled participants who received at least one dose of study drug. Censored participants: Abemaciclib=70.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Overall Survival (OS) | 22.32 Months |
Secondary
Percentage of Participants With CR, PR or SD (Disease Control Rate [DCR])
Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (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: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib | Percentage of Participants With CR, PR or SD (Disease Control Rate [DCR]) | 67.4 Percentage of participants |
Secondary
Percentage of Participants With Tumor Response of Stable Disease (SD) for at Least 6 Months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate)
Clinical benefit rate defined as percentage of patients 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: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 14 Months)
Population: All enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib | Percentage of Participants With Tumor Response of Stable Disease (SD) for at Least 6 Months, Partial Response (PR) or Complete Response (CR) (Clinical Benefit Rate) | 42.4 Percentage of participants |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20
Area Under the Concentration versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) was evaluated for Abemaciclib and Metabolites M2 and M20
Time frame: Cycle 1 Day 1 pre dose, Cycle 1 Day 15 4 hours (h) and 7 h post dose, Cycle 2 Day 1 pre dose and 3 h post dose, Cycle 3 Day1 pre dose
Population: All enrolled participants who received at least one dose of study drug (Abemaciclib) with evaluable Abemaciclib, M2 and M20 pharmacokinetic (PK) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | Abemaciclib | 3510 Nanograms*hour/milliliters (ng*h/mL)] | Geometric Coefficient of Variation 38 |
| Abemaciclib | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | M20 | 2750 Nanograms*hour/milliliters (ng*h/mL)] | Geometric Coefficient of Variation 55 |
| Abemaciclib | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) for Abemaciclib and Metabolites M2 and M20 | M2 | 1620 Nanograms*hour/milliliters (ng*h/mL)] | Geometric Coefficient of Variation 55 |
Secondary
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 first dose, 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: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 27 Months)
Population: All enrolled participants who received at least one dose of study drug. Censored participants: Abemaciclib=35.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib | Progression Free Survival (PFS) | 6.0 Months |