MONARCH 2: A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02107703
• Collaborator: (none)
• Enrollment: 669
• Locations: 142
• Arms: 3
• Anticipated Duration (Months): 114.3
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant.

For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Abemaciclib; Drug: Fulvestrant; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 669 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: MONARCH 2: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without Abemaciclib, a CDK4/6 Inhibitor, for Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer
• Actual Study Start Date: Jul 22, 2014
• Actual Primary Completion Date: Feb 14, 2017
• Anticipated Study Completion Date: Jan 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abemaciclib + Fulvestrant 150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219 ; Drug: Fulvestrant; Administered IM
Placebo Comparator: Placebo + Fulvestrant Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Fulvestrant; Administered IM; Drug: Placebo; Administered Orally
Experimental: Abemaciclib + Fulvestrant (Endocrine Naïve Cohort) 150 milligrams mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219 ; Drug: Fulvestrant; Administered IM

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 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 Outcome Measures

1. Overall Survival (OS) [From Date of Randomization until Death Due to Any Cause (Up To 80 Months)]

   OS defined as the time from the date of randomization 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.

2. Percentage of Participants Achieving 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 31 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. 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.

3. Duration of Response (DOR) [From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 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. 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.

4. Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) [From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 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. 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.

5. Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR]) [From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)]

   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 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.PD was at least a 20% increase in 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.

6. Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf) [Baseline, End of Study (Up To 31 Months)]

   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). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.

7. Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 [Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose]

   Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC[0-∞]) was evaluated for Abemaciclib and Metabolites M2 and M20.

8. Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L) [Baseline, End of Study (Up To 31 Months)]

   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 100mm, 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.

9. Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [Baseline, Short Term Follow Up (Up To 31 Months)]

   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, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

10. Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire [Baseline, Short Term Follow Up (Up To 31 Months)]

    EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Have a diagnosis of HR+, HER2- breast cancer

• Have locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:

• relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression

• relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression

• relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease

• presented de novo with metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease

• for the endocrine naïve cohort: Must not have received prior endocrine therapy in current or prior disease setting

• Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin

• Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist

• Have either measurable disease or nonmeasurable bone only disease

• Have a performance status ≤1 on the ECOG scale

• Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy

Exclusion Criteria

• Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease

• Have clinical evidence or history of central nervous system metastasis

• Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor. For the endocrine naïve cohort: In addition, have received treatment with any prior endocrine therapy

• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively

• Have received recent (within 28 days prior to randomization) yellow fever vaccination

• Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)

• Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest

• Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years

• Have received an autologous or allogeneic stem-cell transplant

• Have active bacterial or fungal infection, or detectable viral infection

• Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B (RANK) ligand targeted agents <7 days prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	Clopton Clinic	Jonesboro	Arkansas	United States	72401
3	Southern California Permanente Medical Group	Bellflower	California	United States	90706
4	Univ of California San Francisco	San Francisco	California	United States	94115
5	Southern California Permanente Medical Group	San Marcos	California	United States	92078
6	Stanford University Clinic	Stanford	California	United States	94305
7	Rocky Mountain Cancer Center	Aurora	Colorado	United States	80012
8	Holy Cross Hospital Inc.	Fort Lauderdale	Florida	United States	33308
9	Florida Cancer Specialists	Fort Myers	Florida	United States	33916
10	Advanced Medical Specialties	Miami	Florida	United States	33176
11	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
12	H Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
13	Palm Beach Cancer Institue	West Palm Beach	Florida	United States	33401
14	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
15	Harbin Clinic	Rome	Georgia	United States	30165
16	Quincy Medical Group	Quincy	Illinois	United States	62301
17	Community Clinical Research Center	Anderson	Indiana	United States	46011
18	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
19	Breslin Cancer Center	Lansing	Michigan	United States	48910
20	Minnesota Oncology/Hematology PA	Minneapolis	Minnesota	United States	55404
21	Freeman Cancer Institute	Joplin	Missouri	United States	64804
22	St Lukes Hospital	Kansas City	Missouri	United States	64111
23	Washington University Medical Center	Saint Louis	Missouri	United States	63110
24	Billings Clinic Research Center	Billings	Montana	United States	59101
25	Oncology Hematology West	Omaha	Nebraska	United States	68130
26	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0001
27	Mount Sinai School of Medicine Dermatology Clinical Trials	New York	New York	United States	10029
28	Columbia University College of Phys & Surgeons	New York	New York	United States	10032
29	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
30	Rochester General Hospital	Rochester	New York	United States	14621
31	Novant Health, Oncology Research Institute	Winston-Salem	North Carolina	United States	27103
32	Sandford Research/USD	Sioux Falls	North Dakota	United States	57104
33	SMO Sanford Research	Sioux Falls	North Dakota	United States	57104
34	Tulsa Cancer Institute, PLLC	Tulsa	Oklahoma	United States	74146
35	Sanford Research/USD	Sioux Falls	South Dakota	United States	57104
36	The Jones Clinic	Germantown	Tennessee	United States	38138
37	The Boston Baskin Cancer Group	Memphis	Tennessee	United States	38120
38	SMO Sarah Cannon Research Inst.	Nashville	Tennessee	United States	37203
39	Texas Oncology Cancer Center	Austin	Texas	United States	78731
40	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Bedford	Texas	United States	76022
41	Texas Oncology Fort Worth	Fort Worth	Texas	United States	76104
42	Texas Oncology-Memorial City	Houston	Texas	United States	77024
43	Baylor College of Medicine	Houston	Texas	United States	77030
44	Oncology Consultants Cancer Center	Houston	Texas	United States	77030
45	Texas Oncology-Plano East	Plano	Texas	United States	75075
46	SMO US Oncology	The Woodlands	Texas	United States	77380
47	Tyler Cancer Center	Tyler	Texas	United States	75702
48	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
49	Fletcher Allen Health Care	Burlington	Vermont	United States	05405
50	Oncology and Hematology Associates of Southwest Virginia Inc	Salem	Virginia	United States	24153
51	Columbia Basin Hematology & Oncology	Kennewick	Washington	United States	99336
52	St Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
53	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	East Bentleigh		Australia	3165
54	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kurralta Park		Australia	5037
55	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	South Brisbane		Australia	4101
56	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Southport		Australia	4215
57	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Subiaco		Australia	6008
58	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Brussel		Belgium	1090
59	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Edegem		Belgium	2650
60	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leuven		Belgium	3000
61	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Liège		Belgium	4000
62	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Calgary	Alberta	Canada	T2N 4N2
63	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	London	Ontario	Canada	N6A 4L6
64	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Toronto	Ontario	Canada	M5B 1W8
65	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Aalborg		Denmark	DK-9000
66	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Herlev		Denmark	2730
67	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Roskilde		Denmark	4000
68	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oulu		Finland	90210
69	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tampere		Finland	33521
70	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Turku		Finland	20520
71	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Besancon		France	25030
72	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Clermont-Ferrand		France
73	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Chaussee Saint Victor		France	41260
74	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Le Mans		France	72000
75	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Augsburg		Germany	86150
76	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	20249
77	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ludwigsburg		Germany	71640
78	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Munich		Germany	80337
79	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tübingen		Germany	72076
80	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Athens		Greece	11522
81	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chania		Greece	73300
82	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Heraklion		Greece	71110
83	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Patras		Greece	26504
84	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bologna		Italy	40139
85	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cona		Italy	44124
86	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Padova		Italy	35128
87	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rome		Italy	00144
88	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bunkyo-ku		Japan	113-8677
89	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chiba		Japan	260-8717
90	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chuo-Ku		Japan	104-0045
91	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	830-0013
92	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kagoshima		Japan	892-0833
93	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kashiwa		Japan	277 8577
94	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kawasaki		Japan	216-8511
95	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kitaadachi-Gun		Japan	362-0806
96	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Koto-ku		Japan	135-8550
97	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kurume		Japan	830-0013
98	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kyoto		Japan	606-8507
99	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Matsuyama		Japan	791-0280
100	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagoya		Japan	464-8681
101	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Niigata		Japan	951-8566
102	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nishinomiya		Japan	663-8501
103	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka		Japan	540-0006
104	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sapporo		Japan	003-0804
105	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shimotsuke		Japan	329- 0498
106	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chungbuk		Korea, Republic of	361-711
107	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gyeonggi-Do		Korea, Republic of	463-070
108	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Incheon		Korea, Republic of	400-711
109	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul		Korea, Republic of	138-736
110	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ulsan-Si		Korea, Republic of	682-714
111	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leon		Mexico	37000
112	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico City		Mexico	14080
113	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mexico		Mexico	03310
114	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64710
115	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nuevo Leon		Mexico	64060
116	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tijuana		Mexico	22010
117	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bialystok		Poland	15-027
118	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdansk		Poland	80-952
119	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz		Poland	90-242
120	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wieliszew		Poland	05-135
121	Puerto Rico Hematology/Oncology Group	Bayamon		Puerto Rico	00959
122	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bucharest		Romania	010976
123	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cluj-Napoca		Romania	400058
124	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Craiova		Romania	200347
125	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Arkhangelsk		Russian Federation	163045
126	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kursk		Russian Federation	305035
127	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moscow		Russian Federation	115478
128	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	St Petersburg		Russian Federation	197022
129	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona		Spain	08035
130	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Elche		Spain	03202
131	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lleida		Spain	25198
132	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid		Spain	28041
133	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Murcia		Spain	30008
134	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Valencia		Spain	46015
135	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Basel		Switzerland	CH-4031
136	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Genève		Switzerland	1211
137	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Thun		Switzerland	3600
138	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kaohsiung		Taiwan	813
139	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kuei Shan Hsiang		Taiwan	33305
140	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taichung		Taiwan	404
141	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei		Taiwan	11217
142	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taoyuan		Taiwan	33378

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 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

Study Documents (Full-Text)

• Study Protocol: JPBL 05 Protocol_Redacted - Apr 1, 2014
• Study Protocol: JPBL 05 Protocol (a)_Redacted - Jan 12, 2015
• Study Protocol: JPBL 05 Protocol (b)_Redacted - Mar 30, 2015
• Study Protocol: JPBL 05 Protocol (c)_Redacted - Oct 27, 2015
• Study Protocol: JPBL 05 Protocol (d)_Redacted - Apr 26, 2016
• Statistical Analysis Plan: version 4 - Jul 8, 2016
• Statistical Analysis Plan: Addendum for Overall Survival Analyses - Aug 25, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02107703
• Other Study ID Numbers: 15362; I3Y-MC-JPBL; 2013-004728-13
• First Posted: Apr 8, 2014
• Last Update Posted: Oct 6, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: MONARCH 2
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Period Title: Overall Study
STARTED	446	223
Received at Least 1 Dose of Study Drug	441	223
COMPLETED	85	48
NOT COMPLETED	361	175

Baseline Characteristics

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant	Total
Arm/Group Description	150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Total of all reporting groups
Overall Participants	446	223	669
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.3 (11.2)	61.1 (11.7)	59.9 (11.4)
Sex: Female, Male (Count of Participants)
Female	446 100%	223 100%	669 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	57 12.8%	25 11.2%	82 12.3%
Not Hispanic or Latino	303 67.9%	162 72.6%	465 69.5%
Unknown or Not Reported	83 18.6%	36 16.1%	119 17.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	18 4%	8 3.6%	26 3.9%
Asian	149 33.4%	65 29.1%	214 32%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 2%	5 2.2%	14 2.1%
White	237 53.1%	136 61%	373 55.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	33 7.4%	9 4%	42 6.3%
Region of Enrollment (Count of Participants)
North America	120 26.9%	58 26%	178 26.6%
Europe	179 40.1%	100 44.8%	279 41.7%
Taiwan	25 5.6%	14 6.3%	39 5.8%
Japan	64 14.3%	31 13.9%	95 14.2%
South Korea	58 13%	20 9%	78 11.7%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	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	From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Abemaciclib=224.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	446	223
Median (95% Confidence Interval) [Months]	16.4	9.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abemaciclib + Fulvestrant, Placebo + Fulvestrant
	Comments	The final analysis was planned at 378 PFS events, which would provide approximately 90% power assuming a hazard ratio (HR) of 0.703 at a one-sided α of 0.025.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0000001
	Comments	This is two sided P value and it is statistically significant.
	Method	Log Rank
	Comments	Log rank test is stratified by endocrine sensitivity and natural of disease by interactive web response system (IWRS).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.553
	Confidence Interval	(2-Sided) 95%; 0.449 to 0.681
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS defined as the time from the date of randomization 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 Randomization until Death Due to Any Cause (Up To 80 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants. Censored participants: Abemaciclib=361.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	446	223
Median (95% Confidence Interval) [Months]	NA	NA

3. Secondary Outcome

Title	Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Description	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. 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.
Time Frame	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 mg Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	446	223
Number (95% Confidence Interval) [Percentage of participants]	35.2 7.9%	16.1 7.2%

4. Secondary Outcome

Title	Duration of Response (DOR)
Description	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. 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.
Time Frame	From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants with response.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	157	36
Median (95% Confidence Interval) [Months]	NA	25.6

5. Secondary Outcome

Title	Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])
Description	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. 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.
Time Frame	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	446	223
Number (95% Confidence Interval) [Percentage of participants]	83.0 18.6%	75.8 34%

6. Secondary Outcome

Title	Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR])
Description	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 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.PD was at least a 20% increase in 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.
Time Frame	From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	446	223
Number (95% Confidence Interval) [Percentage of participants]	72.2 16.2%	56.1 25.2%

7. Secondary Outcome

Title	Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf)
Description	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). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.
Time Frame	Baseline, End of Study (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with a baseline and at least 1 post-baseline result.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	441	223
Least Squares Mean (Standard Error) [score on a scale]	-0.06 (0.07)	0.00 (0.10)

8. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20
Description	Area Under the Plasma 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 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of 150 mg study drug (Abemaciclib) with evaluable Abemaciclib, M2 and M20 PK data.

Arm/Group Title	Abemaciclib + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond.
Measure Participants	326
Abemaciclib	2960 (32.2)
M2	1640 (70.2)
M20	2870 (69.6)

9. Secondary Outcome

Title	Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L)
Description	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 100mm, 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.
Time Frame	Baseline, End of Study (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	441	223
Least Squares Mean (Standard Error) [mm]	0.12 (0.65)	1.16 (0.92)

10. Secondary Outcome

Title	Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Description	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, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.
Time Frame	Baseline, Short Term Follow Up (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	180	126
Global health status	-4.57 (1.55)	-8.15 (1.87)
Functional scale: Physical functioning	-3.76 (1.29)	-7.59 (1.59)
Functional scale: Role functioning	-4.87 (1.73)	-9.58 (2.12)
Functional scale: Emotional functioning	2.38 (1.38)	-2.44 (1.70)
Functional scale: Cognitive functioning	-3.16 (1.29)	-2.96 (1.58)
Functional scale: Social functioning	-4.62 (1.61)	-4.78 (1.97)
Symptom scale: Fatigue	5.01 (1.45)	7.83 (1.78)
Symptom scale: Nausea and vomiting	2.81 (1.35)	6.49 (1.64)
Symptom scale: Pain	-0.47 (1.82)	4.38 (2.21)
Symptom scale: Dyspnoea	5.21 (1.70)	5.39 (2.10)
Symptom scale: Insomnia	-0.04 (1.86)	3.76 (2.27)
Symptom scale: Appetite loss	2.06 (1.85)	6.40 (2.23)
Symptom scale: Constipation	-0.15 (1.59)	3.79 (1.92)
Symptom scale: Diarrhoea	4.14 (1.66)	2.67 (1.99)
Symptom scale: Financial difficulties	0.34 (1.60)	2.85 (1.96)

11. Secondary Outcome

Title	Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire
Description	EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.
Time Frame	Baseline, Short Term Follow Up (Up To 31 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-BR23 data at short term follow up for each BR23 items.

Arm/Group Title	Abemaciclib + Fulvestrant	Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.	Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	182	126
Functional scale: Body image	-2.20 (1.46)	-3.27 (1.83)
Functional scale:Sexual functioning	0.41 (1.00)	-1.60 (1.25)
Functional scale: Future perspective	6.06 (2.06)	10.05 (2.51)
Symptom scale: Systemic therapy side effects	7.23 (1.00)	6.98 (1.22)
Symptom scale: Breast symptoms	-2.10 (0.89)	-0.96 (1.09)
Symptom scale: Arm symptoms	-0.45 (1.29)	0.10 (1.59)

Adverse Events

Time Frame	Up To 31 Months
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	Abemaciclib + Fulvestrant		Placebo + Fulvestrant
Arm/Group Description	150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.		Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
All Cause Mortality
	Abemaciclib + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/441 (2%)		2/223 (0.9%)
Serious Adverse Events
	Abemaciclib + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/441 (22.4%)		24/223 (10.8%)
Blood and lymphatic system disorders
Anaemia	4/441 (0.9%)	4	0/223 (0%)	0
Disseminated intravascular coagulation	1/441 (0.2%)	1	0/223 (0%)	0
Febrile neutropenia	2/441 (0.5%)	2	0/223 (0%)	0
Neutropenia	1/441 (0.2%)	1	1/223 (0.4%)	1
Cardiac disorders
Atrial fibrillation	2/441 (0.5%)	2	0/223 (0%)	0
Atrioventricular block first degree	1/441 (0.2%)	1	0/223 (0%)	0
Cardiac arrest	0/441 (0%)	0	1/223 (0.4%)	2
Cardiac failure	1/441 (0.2%)	1	0/223 (0%)	0
Myocardial infarction	1/441 (0.2%)	1	0/223 (0%)	0
Sinus tachycardia	1/441 (0.2%)	1	0/223 (0%)	0
Supraventricular tachycardia	1/441 (0.2%)	1	0/223 (0%)	0
Ventricular tachycardia	1/441 (0.2%)	1	1/223 (0.4%)	1
Gastrointestinal disorders
Abdominal pain	5/441 (1.1%)	5	1/223 (0.4%)	1
Ascites	1/441 (0.2%)	1	1/223 (0.4%)	2
Diarrhoea	7/441 (1.6%)	7	0/223 (0%)	0
Enterocolitis	1/441 (0.2%)	1	0/223 (0%)	0
Gastritis	1/441 (0.2%)	1	1/223 (0.4%)	1
Intestinal obstruction	1/441 (0.2%)	1	0/223 (0%)	0
Nausea	5/441 (1.1%)	5	1/223 (0.4%)	1
Oesophageal pain	0/441 (0%)	0	1/223 (0.4%)	1
Volvulus	1/441 (0.2%)	1	0/223 (0%)	0
Vomiting	2/441 (0.5%)	2	0/223 (0%)	0
General disorders
Malaise	1/441 (0.2%)	1	0/223 (0%)	0
Multiple organ dysfunction syndrome	1/441 (0.2%)	1	0/223 (0%)	0
Non-cardiac chest pain	1/441 (0.2%)	1	0/223 (0%)	0
Oedema peripheral	1/441 (0.2%)	1	0/223 (0%)	0
Pyrexia	3/441 (0.7%)	4	0/223 (0%)	0
Surgical failure	1/441 (0.2%)	1	0/223 (0%)	0
Hepatobiliary disorders
Cholangitis	1/441 (0.2%)	1	0/223 (0%)	0
Cholecystitis	3/441 (0.7%)	3	0/223 (0%)	0
Drug-induced liver injury	2/441 (0.5%)	4	0/223 (0%)	0
Hepatic failure	2/441 (0.5%)	3	0/223 (0%)	0
Hepatic function abnormal	2/441 (0.5%)	4	0/223 (0%)	0
Immune system disorders
Hypersensitivity	1/441 (0.2%)	1	1/223 (0.4%)	1
Sarcoidosis	1/441 (0.2%)	1	0/223 (0%)	0
Infections and infestations
Bartholin's abscess	1/441 (0.2%)	1	0/223 (0%)	0
Cellulitis	1/441 (0.2%)	1	0/223 (0%)	0
Enterocolitis infectious	2/441 (0.5%)	2	0/223 (0%)	0
Gastroenteritis	1/441 (0.2%)	1	0/223 (0%)	0
Kidney infection	0/441 (0%)	0	1/223 (0.4%)	1
Lower respiratory tract infection	1/441 (0.2%)	1	0/223 (0%)	0
Lung infection	7/441 (1.6%)	8	0/223 (0%)	0
Mastitis	1/441 (0.2%)	1	0/223 (0%)	0
Osteomyelitis	1/441 (0.2%)	1	0/223 (0%)	0
Pyelonephritis acute	1/441 (0.2%)	1	0/223 (0%)	0
Salmonella bacteraemia	0/441 (0%)	0	1/223 (0.4%)	1
Sepsis	6/441 (1.4%)	9	1/223 (0.4%)	1
Skin infection	3/441 (0.7%)	3	1/223 (0.4%)	1
Soft tissue infection	1/441 (0.2%)	1	0/223 (0%)	0
Upper respiratory tract infection	0/441 (0%)	0	1/223 (0.4%)	1
Urinary tract infection	2/441 (0.5%)	2	0/223 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/441 (0.2%)	1	0/223 (0%)	0
Fall	2/441 (0.5%)	2	0/223 (0%)	0
Fracture	3/441 (0.7%)	3	1/223 (0.4%)	1
Hip fracture	0/441 (0%)	0	1/223 (0.4%)	1
Limb injury	1/441 (0.2%)	1	0/223 (0%)	0
Wound complication	3/441 (0.7%)	3	0/223 (0%)	0
Wrist fracture	1/441 (0.2%)	1	0/223 (0%)	0
Investigations
Alanine aminotransferase increased	1/441 (0.2%)	1	0/223 (0%)	0
Aspartate aminotransferase increased	1/441 (0.2%)	1	0/223 (0%)	0
Blood alkaline phosphatase increased	1/441 (0.2%)	1	0/223 (0%)	0
Blood bilirubin increased	1/441 (0.2%)	1	0/223 (0%)	0
Blood creatinine increased	3/441 (0.7%)	3	0/223 (0%)	0
Blood follicle stimulating hormone abnormal	1/441 (0.2%)	1	0/223 (0%)	0
Electrocardiogram qt prolonged	1/441 (0.2%)	1	0/223 (0%)	0
Hormone level abnormal	1/441 (0.2%)	1	0/223 (0%)	0
Oestradiol abnormal	1/441 (0.2%)	1	0/223 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/441 (0.2%)	1	1/223 (0.4%)	2
Dehydration	3/441 (0.7%)	3	1/223 (0.4%)	1
Hyperglycaemia	1/441 (0.2%)	1	1/223 (0.4%)	1
Hypocalcaemia	1/441 (0.2%)	1	0/223 (0%)	0
Hypokalaemia	1/441 (0.2%)	1	0/223 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/441 (0.5%)	2	2/223 (0.9%)	2
Bone pain	1/441 (0.2%)	1	1/223 (0.4%)	1
Muscular weakness	2/441 (0.5%)	2	0/223 (0%)	0
Musculoskeletal chest pain	1/441 (0.2%)	1	0/223 (0%)	0
Musculoskeletal pain	1/441 (0.2%)	1	0/223 (0%)	0
Myositis	1/441 (0.2%)	1	0/223 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign bone neoplasm	1/441 (0.2%)	1	0/223 (0%)	0
Colon cancer	1/441 (0.2%)	1	0/223 (0%)	0
Tumour pain	1/441 (0.2%)	1	0/223 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/441 (0.2%)	1	0/223 (0%)	0
Depressed level of consciousness	1/441 (0.2%)	2	1/223 (0.4%)	1
Dizziness	2/441 (0.5%)	2	0/223 (0%)	0
Headache	2/441 (0.5%)	2	0/223 (0%)	0
Neuropathy	0/441 (0%)	0	1/223 (0.4%)	1
Syncope	1/441 (0.2%)	1	1/223 (0.4%)	1
Psychiatric disorders
Confusional state	1/441 (0.2%)	1	0/223 (0%)	0
Renal and urinary disorders
Acute kidney injury	2/441 (0.5%)	2	0/223 (0%)	0
Chronic kidney disease	1/441 (0.2%)	1	0/223 (0%)	0
Urinary retention	1/441 (0.2%)	1	0/223 (0%)	0
Reproductive system and breast disorders
Pelvic pain	1/441 (0.2%)	1	0/223 (0%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/441 (0%)	0	1/223 (0.4%)	1
Chronic obstructive pulmonary disease	1/441 (0.2%)	1	0/223 (0%)	0
Dyspnoea	6/441 (1.4%)	7	2/223 (0.9%)	3
Pleural effusion	2/441 (0.5%)	2	5/223 (2.2%)	5
Pneumonitis	4/441 (0.9%)	5	0/223 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/441 (0.2%)	1	0/223 (0%)	0
Surgical and medical procedures
Bartholin's cyst removal	1/441 (0.2%)	1	0/223 (0%)	0
Cholecystectomy	1/441 (0.2%)	1	0/223 (0%)	0
Vascular disorders
Embolism	9/441 (2%)	10	1/223 (0.4%)	1
Lymphoedema	0/441 (0%)	0	1/223 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Abemaciclib + Fulvestrant		Placebo + Fulvestrant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	432/441 (98%)		187/223 (83.9%)
Blood and lymphatic system disorders
Anaemia	127/441 (28.8%)	342	8/223 (3.6%)	11
Leukopenia	125/441 (28.3%)	501	4/223 (1.8%)	9
Lymphopenia	32/441 (7.3%)	91	1/223 (0.4%)	7
Neutropenia	203/441 (46%)	808	8/223 (3.6%)	14
Thrombocytopenia	69/441 (15.6%)	154	6/223 (2.7%)	7
Eye disorders
Lacrimation increased	29/441 (6.6%)	33	3/223 (1.3%)	3
Gastrointestinal disorders
Abdominal pain	152/441 (34.5%)	267	34/223 (15.2%)	53
Constipation	60/441 (13.6%)	74	30/223 (13.5%)	41
Diarrhoea	380/441 (86.2%)	1182	55/223 (24.7%)	85
Dry mouth	30/441 (6.8%)	32	14/223 (6.3%)	14
Dyspepsia	27/441 (6.1%)	30	10/223 (4.5%)	11
Nausea	198/441 (44.9%)	351	50/223 (22.4%)	69
Stomatitis	67/441 (15.2%)	95	23/223 (10.3%)	27
Vomiting	114/441 (25.9%)	193	23/223 (10.3%)	38
General disorders
Chills	25/441 (5.7%)	29	1/223 (0.4%)	1
Fatigue	176/441 (39.9%)	288	60/223 (26.9%)	79
Influenza like illness	33/441 (7.5%)	50	15/223 (6.7%)	18
Injection site reaction	36/441 (8.2%)	47	22/223 (9.9%)	40
Oedema peripheral	50/441 (11.3%)	61	15/223 (6.7%)	16
Pain	23/441 (5.2%)	29	8/223 (3.6%)	9
Pyrexia	46/441 (10.4%)	69	13/223 (5.8%)	14
Infections and infestations
Upper respiratory tract infection	49/441 (11.1%)	58	17/223 (7.6%)	24
Urinary tract infection	38/441 (8.6%)	52	6/223 (2.7%)	6
Investigations
Alanine aminotransferase increased	58/441 (13.2%)	108	12/223 (5.4%)	26
Aspartate aminotransferase increased	54/441 (12.2%)	93	15/223 (6.7%)	28
Blood creatinine increased	51/441 (11.6%)	109	1/223 (0.4%)	1
Weight decreased	46/441 (10.4%)	76	5/223 (2.2%)	8
Metabolism and nutrition disorders
Decreased appetite	116/441 (26.3%)	166	26/223 (11.7%)	28
Hypokalaemia	29/441 (6.6%)	62	5/223 (2.2%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	51/441 (11.6%)	92	32/223 (14.3%)	49
Back pain	41/441 (9.3%)	55	26/223 (11.7%)	33
Bone pain	21/441 (4.8%)	24	15/223 (6.7%)	19
Muscular weakness	46/441 (10.4%)	83	13/223 (5.8%)	17
Myalgia	33/441 (7.5%)	40	13/223 (5.8%)	16
Pain in extremity	35/441 (7.9%)	73	7/223 (3.1%)	9
Nervous system disorders
Dizziness	54/441 (12.2%)	81	13/223 (5.8%)	15
Dysgeusia	79/441 (17.9%)	105	6/223 (2.7%)	7
Headache	88/441 (20%)	147	34/223 (15.2%)	65
Neuropathy	32/441 (7.3%)	38	21/223 (9.4%)	25
Psychiatric disorders
Depression	23/441 (5.2%)	25	8/223 (3.6%)	11
Insomnia	31/441 (7%)	36	17/223 (7.6%)	20
Respiratory, thoracic and mediastinal disorders
Cough	59/441 (13.4%)	69	25/223 (11.2%)	28
Dyspnoea	45/441 (10.2%)	53	23/223 (10.3%)	26
Oropharyngeal pain	21/441 (4.8%)	22	12/223 (5.4%)	13
Skin and subcutaneous tissue disorders
Alopecia	69/441 (15.6%)	82	4/223 (1.8%)	4
Dry skin	38/441 (8.6%)	43	3/223 (1.3%)	6
Pruritus	57/441 (12.9%)	70	13/223 (5.8%)	14
Rash	48/441 (10.9%)	70	10/223 (4.5%)	13
Vascular disorders
Hot flush	46/441 (10.4%)	67	22/223 (9.9%)	25

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.