A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer

Breast Cancer Clinical Trial

— MONARCH 3  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Nonsteroidal Aromatase Inhibitors (Anastrozole or Letrozole) Plus LY2835219, a CDK4/6 Inhibitor, or Placebo in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer With No Prior Systemic Therapy in This Disease Setting

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02246621
• Other study ID #: 15417
• Secondary ID: I3Y-MC-JPBM2014-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 6, 2014
• Est. completion date: December 16, 2024

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate how effective nonsteroidal aromatase inhibitors (NSAI) plus abemaciclib are in postmenopausal women with breast cancer. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 493
• Est. completion date: December 16, 2024
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer

• Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease

• Have postmenopausal status

• Have either measurable disease or nonmeasurable bone-only disease

• Have a performance status =1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have adequate organ function

• Have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture prior to randomization and recovered from the acute effects of therapy

• Are able to swallow capsules

Exclusion Criteria:

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis

• Have inflammatory breast cancer

• Have clinical evidence or a history of central nervous system (CNS) metastasis

• Are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer

• Have received prior (neo)adjuvant endocrine therapy with a disease-free interval =12 months from completion of treatment

• Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer

• Have received prior treatment with everolimus

• Have received prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)

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

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

• Have had major surgery within 14 days prior to randomization

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Abemaciclib
Administered orally
• Anastrozole
Administered orally
• Letrozole
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Barwon Health - The Geelong Hospital	Geelong	Victoria
Australia	St. John of God Murdoch Hospital	Murdoch	Western Australia
Australia	Mater Adult Hospital Brisbane	South Brisbane	Queensland
Australia	St Vincent's Hospital	Sydney	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universitaet Graz	Graz	Steiermark
Austria	Medizinische Universitaet Innsbruck	Innsbruck	Tirol
Austria	Ordensklinikum Linz	Linz	Oberösterreich
Austria	Medizinische Universität Wien	Vienna	Wien
Belgium	Institut Jules Bordet	Anderlecht	Bruxelles-Capitale, Région De
Belgium	Cliniques universitaires Saint-Luc	Bruxelles	Brussel
Belgium	Grand Hopital de Charleroi-Site Notre-Dame	Charleroi
Belgium	CHU UCL Namur/Site Sainte Elisabeth	Namur
Belgium	AZ Delta	Roeselare
Belgium	Iridium Kankernetwerk Wilrijk en Antwerp	Wilrijk	Antwerpen
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal (CIUSSS NÎM) - H -T	Montreal	Quebec
Canada	Hopital Notre Dame	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Lakeridge Health	Oshawa	Ontario
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Hopital du Saint-Sacrement	Quebec
Canada	Princess Margaret Hospital (Ontario)	Toronto	Ontario
France	CHU de Besancon Hopital Jean Minjoz	Besancon Cedex
France	Polyclinique Bordeaux Nord	Bordeaux	Aquitaine
France	Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan	Brest	Bretagne
France	Centre Georges François Leclerc	Dijon	Côte-d'Or
France	CHD Vendee	La Roche Sur Yon	Vendée
France	Centre Leon Berard	Lyon	Rhône-Alpes
France	Centre de Cancérologie du Grand Montpellier	Montpellier	Languedoc-Roussillon
France	Polyclinique de Gentilly	Nancy	Meurthe-et-Moselle
France	Institut de Cancérologie de l'Ouest	Saint Herblain	Loire-Atlantique
France	Centre Hospitalier de Saint-Brieuc - Hôpital Yves Le Foll	Saint-Brieuc	Côtes-d'Armor
Germany	Marien-Hospital Düsseldorf	Düsseldorf	Nordrhein-Westfalen
Germany	Facharztzentrum Eppendorf	Hamburg
Germany	Kath. Marienkrankenhaus gGmbH	Hamburg
Germany	Lübecker Onkologische Schwerpunktpraxis	Lubeck	Schleswig-Holstein
Germany	Klinikum Ludwigsburg	Ludwigsburg	Baden-Württemberg
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Helios Dr. Horst Schmidt Kliniken	Wiesbaden	Hessen
Greece	Alexandra Hospital	Athens	Attikí
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa	?eifa
Israel	Hadassah Medical Center	Jerusalem	Yerushalayim
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah-Tikva	HaMerkaz
Israel	Sheba Medical Center	Ramat Gan	HaMerkaz
Israel	Kaplan Medical Center	Rehovot	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Ospedale Bellaria - Azienda USL di Bologna	Bologna
Italy	Ospedale Perrino	Brindisi	BR
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Azienda Ospedaliero Universitaria di Ferrara	Cona	Ferrara
Italy	Ospedale San Martino	Genova	Liguria
Italy	Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte	Messina
Italy	Ospedale Sacro Cuore Don G. Calabria	Negrar Di Valpolicella	Verona
Italy	Nuovo Ospedale di Prato-S.Stefano	Prato	Toscana
Italy	Policlinico Ospedale S. Andrea	Roma
Italy	Azienda Ospedaliera Santa Maria Terni	Terni
Japan	Tokyo Met Cancer & Infectious Diseases Center Komagome Hp	Bunkyo-ku	Tokyo
Japan	Chiba cancer center	Chiba-shi	Chiba
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hiroshima City Hospital	Hiroshima
Japan	Saitama Prefectural Cancer Center	Kitaadachi-Gun	Saitama
Japan	Kurume General Hospital	Kurume	Fukuoka
Japan	Kyoto University Hospital	Kyoto
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Tominaga Hospital	Nagaizumi	Shizuoka
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Hyogo College of Medicine	Nishinomiya	Hyogo
Japan	National Hospital Organization Osaka Medical Center	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital- Osakasayama Campus	Osaka-sayama	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Jichi Medical University Hospital	Shimotsuke	Tochigi
Japan	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Japanese Foundation for Cancer Research	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	Kanagawa cancer center	Yokohama	Kanagawa
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center	Goyang-Si	Kyonggi-do
Korea, Republic of	Inha University Hospital	Incheon	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Korea, Republic of	Ulsan University Hospital	Ulsan	Ulsan-Kwangyokshi
Mexico	Cancerología	Colinas Del Cimatario	Queretaro
Mexico	Centro Oncologico Belenus	Cuernavaca	Morelos
Mexico	Hospital Civil Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Centro de Estudios Y Prevencion Del Cancer	Juchitan	Oaxaca
Mexico	Fundacion Rodolfo Padilla AC	Leon	Guanajuato
Mexico	Superare Centro de Infusion	Mexico	Federal District
Mexico	Grupo Medico Camino Sc	Mexico City	Distrito Federal
Mexico	Hospital La Raza	Mexico City	Distrito Federal
Mexico	Clinica Oncológica San Francisco	Torreon	Coahuila
Netherlands	Haga Ziekenhuis locatie Leyweg	Den Haag	Zuid-Holland
Netherlands	Leids Universitair Medisch Centrum	Leiden
New Zealand	Auckland City Hospital	Auckland
Puerto Rico	San Juan Ccop	San Juan
Russian Federation	Arkhangelsk Clinical Oncological Dispensary	Arkhangelsk	Arkhangel'skaya Oblast'
Russian Federation	Republic Oncology Dispensary of MoH of Republic Tatarstan	Kaznan	Russia
Russian Federation	European Medical Center	Moscow
Russian Federation	Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF	Moscow	Moskva
Russian Federation	Clinic Complex	Saint-Petersburg
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary	Saint-Petersburg
Russian Federation	Rosmedtech Scientific Research Institute of Oncology	St. Petersburg
Slovakia	Onkologicky Ustav sv. Alzbety	Bratislava	Bratislavský Kraj
Slovakia	Vychodoslovensky Onkologicky ustav a.s.	Kosice	Košický Kraj
Spain	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.	Badajoz
Spain	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	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	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	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.	San Sebastian
Spain	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
Sweden	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.	Gavle
Sweden	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.	Orebro
Sweden	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.	Vasteras
Taiwan	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.	Jhonghe City
Taiwan	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	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.	Pei-Tou
Taiwan	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	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
Turkey	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.	Ankara
Turkey	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.	Edirne
Turkey	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.	Malatya
United Kingdom	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.	Bebbington
United Kingdom	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.	Cambridge
United Kingdom	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.	Manchester
United Kingdom	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.	Sutton
United States	CBCC Global Research, Inc.	Bakersfield	California
United States	Ironwood Cancer & Research Centers	Chandler	Arizona
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	California Cancer Associates Research and Excellence	Fresno	California
United States	St Mary's Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Oncology Consultants P.A.	Houston	Texas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Nebraska Hematology-Oncology	Lincoln	Nebraska
United States	Nebraska Hematology-Oncology, P.C.	Lincoln	Nebraska
United States	Central Coast Medical Oncology Corporation	Los Angeles	California
United States	North Valley Hematology/Oncology Medical Group	Los Angeles	California
United States	Orlando Health, Inc	Los Angeles	California
United States	TRIO-US (Translational Research in Oncology-US)	Los Angeles	California
United States	Joe Arrington Cancer Center	Lubbock	Texas
United States	Lakes Research, LLC	Miami Lakes	Florida
United States	Mount Sinai Cancer Center	New York	New York
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Mayo Clinic in Rochester, Minnesota	Rochester	Minnesota
United States	UCLA Hematology/Oncology - Parkside	Santa Monica	California
United States	Candler Medical Oncology Practice - Statesboro	Savannah	Georgia
United States	Candler Medical Oncology Practice - Statesboro	Savannah	Georgia
United States	Summit Cancer Care	Savannah	Georgia
United States	Highlands Oncology Group	Springdale	Arkansas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Puerto Rico,  Russian Federation,  Slovakia,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (2)

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Tredan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib As Initial Therapy for Advanced B — View Citation

Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, Frenzel M, Hardebeck MC, Cox J, Barriga S, Toi M, Iwata H, Goetz MP. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS defined as the time from the first day of therapy to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of 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.	Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
Secondary	Overall Survival (OS)	OS defined as the time from first dose date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.	Randomization to Progressive Disease or Death Due to Any Cause (Estimated Up to 82 Months)
Secondary	Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.	Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
Secondary	Duration of Response (DoR)	DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date.	CR or PR to Disease Progression or Death Due to Any Cause (Up to 32 Months)
Secondary	Percentage of Participants With CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	DCR was the percentage of participants with a best overall response of CR, PR, or 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.	Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
Secondary	Percentage of Participants With Tumor Response of SD for at Least 6 Months, PR, or CR (Clinical Benefit Rate [CBR])	CBR 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.	Randomization to Progressive Disease or Death Due to Any Cause (Up to 32 Months)
Secondary	Change From Baseline to End of Study in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Functional Scale Scores	EORTC QLQ-C30 v3.0 is 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.Functional scale options are defined on a 7-point scale ranging from 1, "Very poor" to 7, "Excellent". A linear transformation is applied to standardize the raw scores to range between 0 and 100 with higher score indicating better functioning. For functional domains and global health status, higher scores represent a better level of functioning. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.	Baseline, End of Study (Up to 32 Months)
Secondary	Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-C30 Symptom Scale Scores	EORTC QLQ-C30 v3.0 is 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. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For symptoms scales, higher scores indicated greater symptom burden. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline. Small changes are generally defined as at least a 3, 4 or 5 point change from baseline.	Baseline, End of Study (Up to 32 Months)
Secondary	Change From Baseline to End of Study in Symptom Burden on the EORTC QLQ-Breast23 Questionnaire	The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much". All scores are converted to a 0 to 100 scale. A higher score representing a higher ("better") level of functioning (BR23: body image, sexual functioning, future perspective), or a higher ("worse") level of symptoms. Least Square (LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.	Baseline, End of Study (Up to 32 Months)
Secondary	Change From Baseline to End of Study in Health Status on the EuroQuol 5-Dimension 5 Level (EuroQol-5D 5L) Index Value	The EuroQol-5D (version 5L) is a brief self-administered, validated instrument consisting of 2 parts.The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a five level scale (no problem, slight problem, moderate problem, severe problem and extreme problem) with higher levels indicating greater severity/ impairment. Published weights are available that allow for the creation of a single summary score called the EQ-5D index that ranges from 0 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health. Minimally important differences in the EQ-5D index score are 0.06 or greater in cancer patients. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.	Baseline, End of Study (Up to 32 Months)
Secondary	Change From Baseline to End of Study in Health Status on the EuroQol-5D 5L Visual Analog Scale (VAS) Scores Scale	The EuroQol-5D (version 5L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). Minimally important differences in the EQ-5D VAS score are 7 or greater in cancer patients. Least Square(LS) Mean was calculated using Mixed Model Repeated Measures (MMRM) model with treatment, Visit, Treatment*Visit and Baseline.	Baseline, End of Study (Up to 32 Months)
Secondary	Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity [AUC(0-8)] of Abemaciclib and Its Metabolites M2 and M20	Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity [AUC(0-8)] of Abemaciclib and Its Metabolites M2 and M20	Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose
Secondary	PK: Hepatic Clearance of Abemaciclib, and Apparent Hepatic Clearance of Its Metabolites M2 and M20	PK: Hepatic Clearance of Abemaciclib, and apparent hepatic clearance of its Metabolites M2 and M20	Cycle 1 Day 1; 2 to 4 hours (h) post dose, Cycle 2 Day 1; 3 h post dose; 7 h post dose, Cycle 3 Day 1; pre dose, 3 h post dose

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