Trial Outcomes & Findings for A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer (NCT NCT02675231)

Last Updated: 2024-11-26

Results Overview

PFS time was measured from the date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

237 participants

Primary outcome timeframe

Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)

Results posted on

2024-11-26

Participant Flow

Completers included participants who either died due to any cause or were alive and on the study at the conclusion but off treatment.

Participant milestones

Participant milestones
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant 150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Overall Study STARTED	79	79	79
Overall Study Received at Least One Dose of Drug	78	77	72
Overall Study COMPLETED	74	71	74
Overall Study NOT COMPLETED	5	8	5

Reasons for withdrawal

Reasons for withdrawal
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant 150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Overall Study Withdrawal by Subject	2	4	2
Overall Study Lost to Follow-up	3	4	3

Baseline Characteristics

A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.	Total n=237 Participants Total of all reporting groups
Age, Continuous	54.34 years STANDARD_DEVIATION 10.25 • n=5 Participants	54.99 years STANDARD_DEVIATION 11.08 • n=7 Participants	56.77 years STANDARD_DEVIATION 12.37 • n=5 Participants	55.37 years STANDARD_DEVIATION 11.27 • n=4 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	79 Participants n=7 Participants	79 Participants n=5 Participants	237 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	58 Participants n=5 Participants	52 Participants n=7 Participants	56 Participants n=5 Participants	166 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	16 Participants n=7 Participants	11 Participants n=5 Participants	34 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	35 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race (NIH/OMB) White	55 Participants n=5 Participants	53 Participants n=7 Participants	55 Participants n=5 Participants	163 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	27 Participants n=4 Participants
Region of Enrollment Argentina	9 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment United States	20 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants	45 Participants n=4 Participants
Region of Enrollment United Kingdom	9 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment Spain	6 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Greece	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Canada	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment South Korea	11 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment Belgium	5 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	19 Participants n=4 Participants
Region of Enrollment Brazil	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment Italy	2 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Region of Enrollment Mexico	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment France	6 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	27 Participants n=4 Participants
Region of Enrollment Germany	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)

Population: All enrolled participants. Censored participants: Abemaciclib + Trastuzumab + Fulvestrant=23; Abemaciclib + Trastuzumab = 18 and Trastuzumab + Standard of Care Chemotherapy = 27.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Progression Free Survival (PFS)	8.3 Months Interval 5.9 to 12.6	5.7 Months Interval 4.2 to 7.2	5.7 Months Interval 5.4 to 6.9

SECONDARY outcome

Timeframe: Randomization to date of death from any cause assessed at 1 year

Population: All randomized participants (including the censored participants). Number of participants censored were "150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant = 62," "150 mg Abemaciclib + 8 mg/kg Trastuzumab = 62," and "8 mg/kg Trastuzumab + Standard of Care Chemotherapy = 58."

OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 1 year from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants With 1 Year Overall Survival (OS)	77.2 percentage of participants Interval 65.9 to 85.2	77.4 percentage of participants Interval 66.1 to 85.3	69.8 percentage of participants Interval 57.5 to 79.1

SECONDARY outcome

Timeframe: Randomization to date of death from any cause assessed at 2 years

Population: All randomized participants (including the censored participants). Number of participants censored were "150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant = 47," "150 mg Abemaciclib + 8 mg/kg Trastuzumab = 47," and "8 mg/kg Trastuzumab + Standard of Care Chemotherapy = 41."

OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 2 years from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants With 2 Year OS	55.8 percentage of participants Interval 43.5 to 66.4	55.7 percentage of participants Interval 43.4 to 66.3	43.0 percentage of participants Interval 30.9 to 54.5

SECONDARY outcome

Timeframe: Randomization to date of death from any cause assessed at 3 years

Population: All randomized participants (including the censored participants). Number of participants censored were "150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant = 41," "150 mg Abemaciclib + 8 mg/kg Trastuzumab = 37," and "8 mg/kg Trastuzumab + Standard of Care Chemotherapy = 33."

OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive. For each treatment arm OS rate at 3 years from the date of randomization was determined using the OS times and was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants With 3 Year OS	46.7 percentage of participants Interval 34.7 to 57.9	40.2 percentage of participants Interval 28.6 to 51.5	29.9 percentage of participants Interval 19.1 to 41.3

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression (Up To 36 Months)

Population: All enrolled participants.

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.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)	32.9 Percentage of participants Interval 22.5 to 43.3	13.9 Percentage of participants Interval 6.3 to 21.6	13.9 Percentage of participants Interval 6.3 to 21.6

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up To 36 Months)

Population: All enrolled participants who received at least one dose of study drug and achieved CR or PR.Censored participants = 12 in 150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant ; 3 participants in 150 mg Abemaciclib + 8 mg/kg Trastuzumab and 11 participants in 8 mg/kg Trastuzumab + Standard of Care Chemotherapy.

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.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=26 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=11 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=11 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Duration of Response (DoR)	12.5 Months Interval 6.5 to 23.5	9.5 Months Interval 2.8 to 22.7	NA Months Interval 4.1 to The median and upper limit of the 95% CI was not calculated due to the high censoring rate.

SECONDARY outcome

Timeframe: Baseline to Objective Disease Progression (Up To 36 Months)

Population: All enrolled participants.

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.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)	78.5 Percentage of participants Interval 69.4 to 87.5	74.7 Percentage of participants Interval 65.1 to 84.3	67.1 Percentage of participants Interval 56.7 to 77.5

SECONDARY outcome

Timeframe: Date of CR, PR or SD to 6 Months Post CR, PR or SD (Up To 36 Months)

Population: All enrolled participants.

Clinical benefit rate 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.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR)	58.2 Percentage of participants Interval 47.4 to 69.1	45.6 Percentage of participants Interval 34.6 to 56.6	38.0 Percentage of participants Interval 27.3 to 48.7

SECONDARY outcome

Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Population: All enrolled participants.

The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes. Mean Interference Score data is reported here. Least square (LS) Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=79 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=79 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=79 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)	0 units on a scale Standard Error 0.18	0.20 units on a scale Standard Error 0.18	0.31 units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 data for each EORTC QLQ-C30 items.

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. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=72 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=72 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=69 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global health status	-2.9 units on a scale Standard Error 1.6	-5.9 units on a scale Standard Error 1.7	-1.9 units on a scale Standard Error 1.8
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Functional scale: Physical functioning	-1.0 units on a scale Standard Error 1.6	-4.4 units on a scale Standard Error 1.6	-4.5 units on a scale Standard Error 1.7
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Functional scale: Role functioning	-2.7 units on a scale Standard Error 2.2	-5.0 units on a scale Standard Error 2.3	-8.2 units on a scale Standard Error 2.4
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Functional scale: Emotional functioning	2.4 units on a scale Standard Error 1.7	-0.4 units on a scale Standard Error 1.8	1.1 units on a scale Standard Error 1.8
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Functional scale: Cognitive functioning	-1.8 units on a scale Standard Error 1.4	-1.1 units on a scale Standard Error 1.5	-1.6 units on a scale Standard Error 1.6
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Functional scale: Social functioning	-0.9 units on a scale Standard Error 1.9	-0.9 units on a scale Standard Error 1.9	-2.4 units on a scale Standard Error 2.0
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Fatigue	1.8 units on a scale Standard Error 1.9	7.0 units on a scale Standard Error 2.0	4.7 units on a scale Standard Error 2.1
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Nausea and vomiting	6.3 units on a scale Standard Error 1.4	5.6 units on a scale Standard Error 1.4	2.2 units on a scale Standard Error 1.5
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Pain	-2.5 units on a scale Standard Error 2.1	3.1 units on a scale Standard Error 2.1	4.3 units on a scale Standard Error 2.2
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Dyspnoea	0.7 units on a scale Standard Error 1.9	2.9 units on a scale Standard Error 2.0	3.7 units on a scale Standard Error 2.1
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Insomnia	-4.4 units on a scale Standard Error 2.1	-1.6 units on a scale Standard Error 2.2	2.0 units on a scale Standard Error 2.3
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Appetite loss	6.3 units on a scale Standard Error 2.3	5.5 units on a scale Standard Error 2.4	2.4 units on a scale Standard Error 2.5
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Constipation	-6.3 units on a scale Standard Error 1.9	-10.5 units on a scale Standard Error 1.9	-3.4 units on a scale Standard Error 2.0
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Diarrhoea	21.5 units on a scale Standard Error 2.2	25.3 units on a scale Standard Error 2.3	2.2 units on a scale Standard Error 2.4
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Symptom scale: Financial difficulties	0.8 units on a scale Standard Error 2.0	-1.9 units on a scale Standard Error 2.1	-3.2 units on a scale Standard Error 2.2

SECONDARY outcome

Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Population: All enrolled participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status.LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=72 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=72 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=68 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score	0.01 units on a scale Standard Error 0.02	-0.01 units on a scale Standard Error 0.02	-0.04 units on a scale Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months)

Population: All enrolled participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L VAS data.

European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=72 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=71 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy n=70 Participants 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)	0.61 millimeter (mm) Standard Error 1.4	-1.64 millimeter (mm) Standard Error 1.4	-0.61 millimeter (mm) Standard Error 1.5

SECONDARY outcome

Timeframe: Cycle(C)1 Day(D)1,C1D15, C2D1, C2D8, C3D1,C3D15, C4D1, C5D1:pre-dose; C1D1, C2D1, C3D1, C4D1, C5D1:post-dose

Population: All enrolled participants who received at least one dose of study drug and had evaluable PK data.

Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) was evaluated. M2 and M20 are 2 major active metabolites of abemaciclib.

Outcome measures

Outcome measures
Measure	150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant n=77 Participants 150 mg abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 mg/kg trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.	150 mg Abemaciclib + 8 mg/kg Trastuzumab n=71 Participants 150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.	8 mg/kg Trastuzumab + Standard of Care Chemotherapy 8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label.
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) Abemaciclib	134 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 77	155 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 53	—
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) M2	72.0 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 120	96.5 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 120	—
Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20) M20	136 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 120	181 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 130	—

Adverse Events

150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant

Serious events: 24 serious events

Other events: 76 other events

Deaths: 52 deaths

150 mg Abemaciclib + 8 mg/kg Trastuzumab

Serious events: 15 serious events

Other events: 75 other events

Deaths: 55 deaths

8 mg/kg Trastuzumab + Standard of Care Chemotherapy

Serious events: 14 serious events

Other events: 68 other events

Deaths: 53 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place