monarchE: Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03155997
• Collaborator: NSABP Foundation Inc (Other)
• Enrollment: 5,637
• Locations: 612
• Arms: 2
• Anticipated Duration (Months): 143.4
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Abemaciclib; Drug: Standard Adjuvant Endocrine Therapy	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 5637 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer
• Actual Study Start Date: Jul 12, 2017
• Actual Primary Completion Date: Mar 16, 2020
• Anticipated Study Completion Date: Jun 24, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 150 mg Abemaciclib + Endocrine Therapy Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Drug: Abemaciclib; Administered orally.; Other Names: LY2835219 ; Drug: Standard Adjuvant Endocrine Therapy; Administered according to label instructions.
Other: Endocrine Therapy Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Drug: Standard Adjuvant Endocrine Therapy; Administered according to label instructions.

Outcome Measures

Primary Outcome Measures

1. Invasive Disease Free Survival (IDFS) [Baseline to Recurrence or Death from Any Cause (Up to 32 Months)]

   IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause.

Secondary Outcome Measures

1. IDFS for Participants With Ki-67 Index ≥20% [Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)]

   Outcome data will be provided after the study is completed.

2. Distant Relapse-Free Survival (DRFS) [Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)]

   Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first.

3. Overall Survival (OS) [Baseline to Death from Any Cause (Approximately 10 Years)]

   Outcome data will be provided after the study is completed.

4. Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib [Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose]

   Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib

5. Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) [Baseline, Follow Up (Approximately 3 Years)]

   Outcome data will be provided after the study is completed.

6. Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) [Baseline, Follow Up (Approximately 3 Years)]]

   Outcome data will be provided after the study is completed.

7. Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [Baseline, Follow Up (Approximately 3 Years)]]

   Outcome data will be provided after the study is completed.

8. Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) [Baseline, Follow Up (Approximately 3 Years)]]

   Outcome data will be provided after the study is completed.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations).

• The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases.

• The participant must have undergone definitive surgery of the primary breast tumor.

• The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization.

• Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence:

• 4 or more positive axillary lymph nodes

• Tumor size of at least 5 centimeters

• Grade 3 defined as at least 8 points on the Bloom Richardson grading system

• Ki-67 index by central analysis of ≥20% on untreated breast tissue

• The participant must be randomized within 16 months from the time of definitive breast cancer surgery.

• The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last.

• Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery.

• Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods.

• The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

• The participant has adequate organ function.

• The participant is able to swallow oral medications.

Exclusion Criteria:

• Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease.

• Participants with inflammatory breast cancer.

• Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded.

• Females who are pregnant or lactating.

• The participant has previously received treatment with any CDK4 and CDK6 inhibitor.

• The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).

• The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene.

• The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.

• The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE).

• The participant has active systemic infections or viral load.

• The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	32594
2	Southern Cancer Center, P.C.	Daphne	Alabama	United States	36526
3	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
4	University of Arizona Cancer Center	Phoenix	Arizona	United States	85004
5	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
6	Arizona Oncology Associates, P.C.	Tempe	Arizona	United States	85284
7	Arizona Oncology Associates, P.C.	Tucson	Arizona	United States	85704
8	The University of Arizona Cancer Center	Tucson	Arizona	United States	85719
9	Yuma Regional Cancer Center	Yuma	Arizona	United States	85364
10	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
11	St. Bernards Medical Center	Jonesboro	Arkansas	United States	72401
12	Beverly Hills Cancer Center	Beverly Hills	California	United States	90211
13	Providence St. Joseph's Medical Center	Burbank	California	United States	91505
14	City of Hope National Medical Center	Duarte	California	United States	91010-0269
15	California Cancer Associates Research and Excellence (cCARE)	Fresno	California	United States	93720
16	Loma Linda University School of Medicine	Loma Linda	California	United States	92354
17	Cedars Sinai Medical Center	Los Angeles	California	United States	90048-5615
18	Pacific Cancer Care	Monterey	California	United States	93940
19	St. Joseph Hospital	Orange	California	United States	92868
20	University of California, Davis - Health Systems	Sacramento	California	United States	95817
21	Kaiser Permanente Medical Group	San Diego	California	United States	92108
22	Univ of California San Francisco	San Francisco	California	United States	94158
23	California Cancer Associates in Research and Excellence	San Marcos	California	United States	92069
24	Sansum Clinic	Santa Barbara	California	United States	93105
25	Dominican Hospital	Santa Cruz	California	United States	95065
26	Kaiser Permanente	Vallejo	California	United States	94589
27	Rocky Mountain Cancer Center	Denver	Colorado	United States	80220
28	Yale University School of Medicine	New Haven	Connecticut	United States	06510
29	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
30	University of Southern Florida School of Medicine	Gainesville	Florida	United States	32610-0296
31	Millennium Oncology	Hollywood	Florida	United States	33024
32	Mayo Clinic-Jacksonville	Jacksonville	Florida	United States	32224
33	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida	United States	33176
34	Ocala Oncology, P.A.	Ocala	Florida	United States	34474
35	Cancer Specialists of North Florida -St Augustine	Saint Augustine	Florida	United States	32086
36	Florida Cancer Specialists	Saint Petersburg	Florida	United States	33705
37	Tallahassee Memorial Cancer Center	Tallahassee	Florida	United States	32308
38	H Lee Moffitt Cancer Center	Tampa	Florida	United States	33612-9497
39	Florida Cancer Specialists	West Palm Beach	Florida	United States	33401
40	Northeast Georgia Cancer Care, LLC	Athens	Georgia	United States	30607
41	Northside Hospital Cancer Institute	Atlanta	Georgia	United States	30342
42	Northwest Georgia Oncology Centers	Marietta	Georgia	United States	30060
43	Summit Cancer Care	Savannah	Georgia	United States	31405
44	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
45	John H. Stroger Hospital of Cook County	Chicago	Illinois	United States	60612
46	Rush University Medical Center	Chicago	Illinois	United States	60612
47	Edward Cancer Center	Naperville	Illinois	United States	60540
48	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
49	Quincy Medical Group	Quincy	Illinois	United States	62301
50	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
51	Community Howard Oncology Center	Kokomo	Indiana	United States	46902
52	Cancer Center of Kansas	Wichita	Kansas	United States	67214
53	Univ of Louisville School of Medicine	Louisville	Kentucky	United States	40202
54	Lady of the Lake Physicians' Group	Baton Rouge	Louisiana	United States	70809
55	Terrebonne General Medical Center	Houma	Louisiana	United States	70360
56	Eastern Maine Medical Center	Brewer	Maine	United States	04412
57	Central Maine Healthcare Corporation	Lewiston	Maine	United States	04240
58	New England Cancer Specialists - Scarborough	Scarborough	Maine	United States	04074
59	Maryland Oncology Hematology, P.A.	Columbia	Maryland	United States	21044
60	Meritus John Marsh Cancer Center	Hagerstown	Maryland	United States	21742
61	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
62	Reliant Medical Group, Inc.	Worcester	Massachusetts	United States	01608
63	Minnesota Oncology/Hematology PA	Minneapolis	Minnesota	United States	55404
64	Mayo Clinic	Rochester	Minnesota	United States	55905-0002
65	Jackson Oncology Associates PLLC	Jackson	Mississippi	United States	39202-2002
66	Research Medical Center	Kansas City	Missouri	United States	64132
67	Cancer Alliance of Nebraska	Omaha	Nebraska	United States	68106
68	Nebraska Methodist Cancer Center	Omaha	Nebraska	United States	68114
69	NCCA- National Cancer Care Alliance	Omaha	Nebraska	United States	68130
70	Oncology Hematology West	Omaha	Nebraska	United States	68130
71	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89052
72	Renown Medical Group	Reno	Nevada	United States	89502
73	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0001
74	Summit Medical Group PA	Florham Park	New Jersey	United States	07932
75	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
76	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey	United States	07652
77	Community Medical Center	Toms River	New Jersey	United States	08755
78	New York Oncology Hematology, P.C	Albany	New York	United States	12206
79	Broome Oncology LLC	Johnson City	New York	United States	13790
80	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
81	Weill Cornell Medical College	New York	New York	United States	10065
82	Vassar Brothers Medical Center	Poughkeepsie	New York	United States	12601
83	SUNY At Stony Brook	Stony Brook	New York	United States	11794
84	White Plains Hospital	White Plains	New York	United States	10601
85	Waverly Hematology Oncology	Cary	North Carolina	United States	27518
86	Margaret R. Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28739
87	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157-1045
88	Aultman Hospital	Canton	Ohio	United States	44710
89	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
90	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
91	Columbus Community Clinical Oncology Program	Columbus	Ohio	United States	43215
92	Oncology Hematology Care Inc	Fairfield	Ohio	United States	45014
93	Hematology Oncology Associates, PC	Medford	Oregon	United States	97504
94	OHSU Knight Cancer Institute	Portland	Oregon	United States	97210
95	Providence Cancer Center Oncology Hematology Care	Portland	Oregon	United States	97213
96	Northwest Cancer Specialists PC	Portland	Oregon	United States	97225
97	Willamette Valley Cancer Institute & research Ctr.	Springfield	Oregon	United States	97477
98	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
99	St. Luke's Hospital & Health Network	Bethlehem	Pennsylvania	United States	18015
100	PinnacleHealth Cancer Institute	Harrisburg	Pennsylvania	United States	17109
101	Albert Einstein Healthcare Network	Philadelphia	Pennsylvania	United States	19141
102	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
103	NSABP Foundation	Pittsburgh	Pennsylvania	United States	15213
104	Univ of Pittsburgh Cancer Inst. (UPCI)	Pittsburgh	Pennsylvania	United States	15213
105	WellSpan Health/York Cancer Center Oncology Research	York	Pennsylvania	United States	17403
106	McLeod Regional Medical Center	Florence	South Carolina	United States	29502
107	Bon Secours Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
108	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
109	Sanford Research/USD	Sioux Falls	South Dakota	United States	57104
110	UT/Erlanger Oncology & Hematology	Chattanooga	Tennessee	United States	37403
111	Sarah Cannon Research Institute SCRI	Chattanooga	Tennessee	United States	37404
112	The West Clinic	Germantown	Tennessee	United States	38138
113	Indian Path Community Hospital	Kingsport	Tennessee	United States	37660
114	Brig Center For Cancer Care and Survivorship	Knoxville	Tennessee	United States	37909
115	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
116	Baptist Cancer Center	Memphis	Tennessee	United States	38120
117	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
118	Tennessee Oncology PLLC	Nashville	Tennessee	United States	37203
119	Texas Oncology - Amarillo	Amarillo	Texas	United States	79106
120	Texas Oncology-Arlington South	Arlington	Texas	United States	76014
121	Texas Oncology Cancer Center	Austin	Texas	United States	78731
122	Texas Oncology - Carrollton	Carrollton	Texas	United States	75010
123	Texas Oncology - Methodist Dallas Cancer Center	Dallas	Texas	United States	75203
124	Texas Oncology - Medical City Dallas	Dallas	Texas	United States	75230
125	Texas Oncology - Dallas Presbyterian Hospital	Dallas	Texas	United States	75231
126	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
127	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390
128	Texas Oncology Denton	Denton	Texas	United States	76210-6857
129	Texas Oncology-El Paso Cancer Treatment Center	El Paso	Texas	United States	79902
130	Texas Oncology Fort Worth	Fort Worth	Texas	United States	76104
131	Oncology Consultants, P.A.	Houston	Texas	United States	77030
132	Texas Oncology - Tyler	Longview	Texas	United States	75601
133	Texas Oncology - McAllen	McAllen	Texas	United States	78503
134	Texas Oncology-McKinney	McKinney	Texas	United States	75071
135	Texas Oncology- Mesquite	Mesquite	Texas	United States	75150
136	Texas Oncology - Paris	Paris	Texas	United States	75460
137	Texas Oncology-Plano East	Plano	Texas	United States	75075
138	Texas Oncology-Plano West	Plano	Texas	United States	75093
139	University of Texas Health Science Center - San Antonio	San Antonio	Texas	United States	78229
140	Texas Oncology - San Antonio Medical Center	San Antonio	Texas	United States	78240
141	Texas Oncology-Sherman	Sherman	Texas	United States	75090-0504
142	Texas Oncology - The Woodlands	The Woodlands	Texas	United States	77380
143	US Oncology	The Woodlands	Texas	United States	77380
144	Texas Oncology Cancer Care and Research Center	Waco	Texas	United States	76712
145	Texas Oncology-Deke Slayton Cancer Center	Webster	Texas	United States	77598-4219
146	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
147	University of Vermont Medical Center	Burlington	Vermont	United States	05401
148	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
149	Hematology Oncology Associates of Fredericksburg Inc.	Fredericksburg	Virginia	United States	22408
150	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
151	Virginia Commonwealth University	Richmond	Virginia	United States	23298
152	Oncology and Hematology Associates of Southwest Virginia Inc	Salem	Virginia	United States	24153
153	Shenandoah Oncology, P.C.	Winchester	Virginia	United States	22601
154	Swedish Medical Center	Seattle	Washington	United States	98104
155	Multicare Health System	Tacoma	Washington	United States	98405
156	Centro de Oncologia e Investigacion Buenos Aires	Berazategui	Buenos Aires	Argentina	B1884BBF
157	Instituto de Investigaciones Clinicas Mar del Plata	Mar del Plata	Buenos Aires	Argentina	B7600FZN
158	Hospital Universitario Austral	Pilar	Buenos Aires	Argentina	B1629ODT
159	Fundacion CENIT para la Investigacion en Neurociencias	Caba	Ciudad Autonoma Buenos Aires	Argentina	C1125ABD
160	Centros de Investigaciones Cli-nicas. Clinica Viedma	Viedma	Rio Negro	Argentina	8500
161	Instituto de Oncologia de Rosario	Rosario	Santa Fe	Argentina	2000
162	Centro Medico San Roque	S.M. De Tucuman	Tucuman	Argentina	T4000IAK
163	Instituto Médico Especializado Alexander Fleming	Buenos Aires		Argentina	1426
164	Instituto de Investigaciones Metabolicas	Buenos Aires		Argentina	C1012AAR
165	Hospital Aleman	Capital Federal		Argentina	C1118AAT
166	Clinica Adventista de Belgrano	Ciudad Autonoma Buenos Aires		Argentina	C1430EGF
167	Centro Oncologico Riojano Integral	La Rioja		Argentina	5300
168	Sanatorio Parque	Salta		Argentina	4400
169	Centro Polivalente de Asistencia e Inv. Clinica CER-San Juan	San Juan		Argentina	5400
170	Centro para la Atencion Integral del Paciente Oncologico	Tucuman		Argentina	4000
171	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
172	Lismore Base Hospital	Lismore	New South Wales	Australia	2480
173	Liverpool Hospital	Liverpool	New South Wales	Australia	2170
174	Calvary Mater Newcastle	Newcastle	New South Wales	Australia	2298
175	Mater Private Hospital	North Sydney	New South Wales	Australia	2291
176	St Vincent's Hospital	Sydney	New South Wales	Australia	2010
177	Westmead Hospital	Westmead	New South Wales	Australia	2145
178	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
179	The Townsville Hospital	Douglas	Queensland	Australia	4814
180	Mater Adult Hospital Brisbane	South Brisbane	Queensland	Australia	4101
181	Gold Coast University Hospital	Southport	Queensland	Australia	4215
182	Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5112
183	Ashford Cancer Centre Research	Kurralta Park	South Australia	Australia	5037
184	Launceston General Hospital	Launceston	Tasmania	Australia	7250
185	Box Hill Hospital	Box Hill	Victoria	Australia	3128
186	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
187	Epworth Research Institute	Richmond	Victoria	Australia	3121
188	Eastern Health, Maroondah Hospital	Ringwood East	Victoria	Australia	3135
189	St John of God Hospital - Subiaco	Subiaco	Western Australia	Australia	6008
190	Breast Cancer Research Centre WA	Nedlands		Australia	6009
191	Universitätsklinikum Graz	Graz	Steiermark	Austria	8036
192	Universitätsklinik Innsbruck	Innsbruck	Tirol	Austria	6020
193	Ordination Dr. Hubalek - Brustzentrum Schwaz	Schwaz	Tirol	Austria	6130
194	Universitätsklinikum Salzburg	Salzburg		Austria	5020
195	AKH	Wien		Austria	1090
196	KH Hietzing mit neurologischem Zentrum Rosenhügel	Wien		Austria	1130
197	Jessa Ziekenhuis	Hasselt	Limburg	Belgium	3500
198	AZ Nikolaas, Campus Moerland	Sint-Niklaas	Oost-Vlaanderen	Belgium	9100
199	Vivalia St Joseph	Arlon		Belgium	6700
200	AZ Klina	Brasschaat		Belgium	2930
201	Algemeen Ziekenhuis St Jan Brugge	Brugge		Belgium	8000
202	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
203	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
204	Hopital De Jolimont	Haine-St.- Paul		Belgium	7100
205	VZW REgional Ziekenhuis Jan Yperman	Ieper		Belgium	8900
206	AZ Groeninge	Kortrijk		Belgium	8500
207	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
208	Centre Hospitalier Universitaire Sart Tilman	Liege		Belgium	4000
209	Clinique St Joseph	Liege		Belgium	4000
210	Hôpital Civil Marie Curie	Lodelinsart		Belgium	6042
211	Clinique St Elisabeth Namur	Namur		Belgium	5000
212	Clinique Saint Pierre Ottignies	Ottignies		Belgium	1340
213	CHU Dinant Godinne - UCL Namur	Yvoir		Belgium	5530
214	Instituto do Cancer do Ceara	Fortaleza	Ceara	Brazil	60430-230
215	Sírio-Libanês Brasilia-Centro de Oncologia-Asa Sul	Brasilia	District Federal	Brazil	70200-730
216	Hospital Araujo Jorge da Assoc. Combate ao Cancer em Goias	Goiania	Goias	Brazil	74605-070
217	Instituto de Cancer de Londrina	Londrina	Parana	Brazil	86015-520
218	CIONC - Centro Integrado de Oncologia de Curitiba	Curitiba	Paraná	Brazil	80810-050
219	Hospital de Caridade Ijui	Ijui	Rio Grande Do Sul	Brazil	98700 000
220	Hospital São Lucas - PUCRS - ONCOLOGY	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
221	Instituto COI de Pesquisa Educação e Gestão	Rio de Janeiro	RJ	Brazil	22793-080
222	Hospital Bruno Born de Lajeado	Lajeado	RS	Brazil	95900
223	Fundação PIO XII	Barretos	Sao Paulo	Brazil	14784-400
224	Hospital de Base Fac de Medicina de Sao Jose do Rio Preto	Sao Jose Rio Preto	Sao Paulo	Brazil	15090-000
225	Instituto do Cancer do Estado de Sao Paulo - ICESP	São Paulo	SP	Brazil	01246-000
226	Hospital das Clinicas da FMRP	Ribeirao Preto	São Paulo	Brazil	14048
227	Faculdade de Medicina do ABC	Santo André	São Paulo	Brazil	09060
228	INCA - Instituto Nacional Do Cancer	Rio De Janeiro		Brazil	20560-120
229	Clinica Onco Star	Sao Paulo		Brazil	04543
230	Soc. Beneficente de Senhoras Hospital Sirio Libanes-Oncology	São Paulo		Brazil	01308-050
231	Clin. Pesq.e Centro Estudos Oncologia Ginecológica e Mamária	São Paulo		Brazil	01317-000
232	Ibcc-Instituto Brasileiro de Controle Do Câncer	São Paulo		Brazil	03102-006
233	Instituto de Assistência Médica ao Servidor Público Estadual	São Paulo		Brazil	04039
234	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
235	North York General Hospital	Toronto	Ontario	Canada	M2K 1E1
236	Humber River Regional Hospital	Toronto	Ontario	Canada	M3M 0B2
237	St Michaels Hospital	Toronto	Ontario	Canada	M5B 1W8
238	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3E4
239	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
240	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec	Canada	H4J 1C5
241	CHU de Quebec-Hopital de Saint-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
242	Centre Hospitalier Universitaire de Sherbrooke - CHUS	Sherbrooke	Quebec	Canada	J1H 5N4
243	The Fifth Medical Center of PLA General Hospital	Beijing	Beijing	China	100071
244	Fujian Medical University Union Hospital	Fuzhou	Fujian	China	350001
245	Guangdong Provincial People's Hospital	Guangzhou	Guangdong	China	510080
246	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510080
247	The First Affiliated Hospital, Sun-Yat Sen University	Guangzhou	Guangdong	China	510080
248	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
249	Henan Cancer Hospital	Zhengzhou	Henan	China	450008
250	Hunan Cancer Hospital	Changsha	Hunan	China	410013
251	Jiangsu Cancer Hospital	Nanjing	Jiangsu	China	210009
252	Jiangsu Province Hospital	Nanjing	Nanjing	China	210029
253	Shandong Cancer Hospital	JiNan	Shandong	China
254	Zhejiang Cancer Hospital	Hang Zhou	Zhejiang	China	310022
255	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
256	Beijing Cancer Hospital	Beijing		China	100142
257	Ruijin Hospital Affiliated to Shanghai Jiao Tong University	Shanghai		China	200025
258	Fudan University Shanghai Cancer Center	Shanghai		China	200030
259	Masarykuv onkologicky ustav	Brno	Czech Republic	Czechia	656 53
260	Nemocnice Horovice	Horovice		Czechia	268 31
261	Fakultni Nemocnice Ostrava	Ostrava		Czechia	708 52
262	Multiscan, s.r.o.	Pardubice		Czechia	532 03
263	FN Plzen Lochotin	Plzen		Czechia	30460
264	Thomayerova Nemocnice	Praha 4 - Krc		Czechia	140 59
265	Odense Universitetshospital	Odense C	Syd	Denmark	5000
266	Aalborg Universitets hospital	Aalborg		Denmark	9000
267	Aarhus Universitetshospital, Aarhus Sygehus	Aarhus C		Denmark	8000
268	Sydvestjysk Sygehus Esbjerg	Esbjerg		Denmark	6700
269	Herlev Hospital	Herlev		Denmark	2730
270	Regionshospitalet Herning	Herning		Denmark	7400
271	Rigshospitalet	København Ø		Denmark	2100
272	Næstved Sygehus	Næstved		Denmark	4700
273	Soenderborg Sygehus	Soenderborg		Denmark	6400
274	Vejle Sygehus	Vejle		Denmark	7100
275	Tampere University Hospital TAYS	Tampere	Pirkanmaa	Finland	33521
276	Satakunta Central Hospital - Oncology	Pori	Satakunta	Finland	28500
277	Helsinki Docrates Cancer Clinic	Helsinki		Finland	00180
278	Keski-Suomen Keskussairaala	Jyväskylä		Finland	40620
279	Kuopio University Hospital	Kuopio		Finland	70210
280	Päijät-Häme Central hospital	Lahti		Finland	15850
281	Oulu University Hospital - Oncology	Oulu		Finland	90220
282	Turku University Central Hospital	Turku		Finland	SF-20520
283	Vaasa Central Hospital	Vaasa		Finland	65130
284	Centre Jean Perrin	Clermont Ferrand BP 392	Cedex 1	France	63011
285	Institut Sainte Catherine	Avignon Cedex 9		France	84918
286	CHU de Besancon Hopital Jean Minjoz	Besancon Cedex		France	25030
287	CHRU de Brest - Hôpital Morvan	Brest		France	29200
288	CHU Henri Mondor	Creteil Cedex		France	94010
289	Centre Georges Francois Leclerc	Dijon Cedex		France	21000
290	Polyclinique De Blois	La Chaussee Saint Victor		France	41260
291	Centre Hospitalier de Vendee Les Oudairies	La Roche Sur Yon		France	85025
292	Clinique Victor Hugo - Centre Jean Bernard	Le Mans		France	72000
293	Centre de Lutte Contre le Cancer Leon Berard	Lyon Cedex 08		France	69373
294	Centre de Cancérologie du Grand Montpellier	Montpellier		France	34070
295	Polyclinique de Gentilly	Nancy		France	54000
296	Institut Curie	Paris CEDEX 05		France	75248
297	Hôpital Privé des Côtes d'Armor- HPCA	Plérin		France	22190
298	Centre Eugene Marquis	Rennes Cedex		France	35042
299	Centre Henri Becquerel	Rouen Cedex		France	76038
300	Institut de Cancérologie de l'Ouest Centre René Gauducheau	Saint Herblain Cedex		France	44805
301	Universitätsklinikum Freiburg	Freiburg im Breisgau	Baden-Württemberg	Germany	79106
302	Onkologische Schwerpunktpraxis	Freiburg im Breisgau	Baden-Württemberg	Germany	79110
303	Praxis für Onkologie	Friedrichshafen	Baden-Württemberg	Germany	88045
304	Klinikum Ludwigsburg	Ludwigsburg	Baden-Württemberg	Germany	71640
305	Universitätsklinikum Tübingen	Tübingen	Baden-Württemberg	Germany	72076
306	Universitätsklinikum Ulm	Ulm	Baden-Württemberg	Germany	89075
307	Hämatologisch-Onkologische Praxis Augsburg	Augsburg	Bavaria	Germany	86150
308	Gesundheitszentrum St. Marien Amberg	Amberg	Bayern	Germany	92224
309	Universitätsklinikum Erlangen	Erlangen	Bayern	Germany	91054
310	Klinikum der Universität München	München	Bayern	Germany	80336
311	Rotkreuzklinikum München - Frauenklinik	München	Bayern	Germany	80637
312	Klinikum Rechts der Isar der TU München	München	Bayern	Germany	81675
313	Agaplesion Markus Krankenhaus	Frankfurt am Main	Hessen	Germany	60431
314	Städtische Kliniken Offenbach am Main	Offenbach am Main	Hessen	Germany	63069
315	Gemeinschaftspraxis für Hämatologie und Onkologie	Langen	Hesse	Germany	63225
316	Franziskus-Hospital Harderberg	Georgsmarienhütte	Niedersachsen	Germany	49124
317	Gynäkologisch-onkologische Schwerpunktpraxis am Pelikanplatz	Hannover	Niedersachsen	Germany	30177
318	Medizinische Hochschule Hannover	Hannover	Niedersachsen	Germany	30625
319	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen	Germany	53105
320	Universitätsklinikum Düsseldorf	Düsseldorf	Nordrhein-Westfalen	Germany	40225
321	Kliniken Essen-Mitte Ev. Huyssens-Stiftung	Essen	Nordrhein-Westfalen	Germany	45136
322	HELIOS Klinikum Krefeld	Krefeld	Nordrhein-Westfalen	Germany	47805
323	Evangelisches Krankenhaus Bethesda Mönchengladbach gGmbH	Mönchengladbach	Nordrhein-Westfalen	Germany	41061
324	Universitätsklinikum Münster	Münster	Nordrhein-Westfalen	Germany	48149
325	St. Elisabeth Gruppe - Marien Hospital Witten	Witten	Nordrhein-Westfalen	Germany	58452
326	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen	Germany	01307
327	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein	Germany	24105
328	SRH Wald-Klinikum Gera gGmbH	Gera	Thüringen	Germany	07548
329	HELIOS Klinikum Emil von Behring	Berlin		Germany	13125
330	Medizinisches Versorgungszentrum Onkologischer Schwerpunkt am Oskar-Helene-Heim	Berlin		Germany	14195
331	Mammazentrum Hamburg Brustklinik am Krankenhaus Jerusalem	Hamburg		Germany	20357
332	Kath. Marienkrankenhaus gGmbH	Hamburg		Germany	22087
333	MVZ Onkologie Barmbek - Asklepios Klinik Barmbek	Hamburg		Germany	22307
334	University General Hospital of Patras	Patras	Achaia	Greece	26504
335	Metropolitan Hospital	Neo Faliro	Athens	Greece	18547
336	General Hospital of Athens 'Alexandra'	Athens	Attica	Greece	115 28
337	Ag. Savvas Hospital	Athens	Attica	Greece	11522
338	Gen Onc Hosp Ag. Anargyroi	N. Kifissia	Attica	Greece	14564
339	University General Hospital of Heraklion	Heraklion	Crete	Greece	71110
340	Bioclinic of Thessaloniki	Thessaloniki	Macedonia	Greece	54622
341	General Hospital of Thessaloniki Papageorgiou	N. Efkarpia	Thessaloniki	Greece	56403
342	Errikos Dynan	Athens		Greece	11526
343	Attikon' University Hospital	Haidari/Athens		Greece	12462
344	University Hospital of Ioannina	Ioannina		Greece	45500
345	Interbalkan Medical Center	Pylaia/Thessaloniki		Greece	57001
346	Euromedica - General Clinic of Thessaloniki	Thessaloniki		Greece	54645
347	Pamela Youde Nethersole Eastern Hospital	Hong Kong		Hong Kong
348	Queen Mary Hospital	Hong Kong		Hong Kong
349	Tuen Mun Hospital	Hong Kong		Hong Kong
350	Queen Elizabeth Hospital	Kowloon		Hong Kong
351	Bacs-Kiskun Megyei Korhaz	Kecskemet	Bacs-Kiskun	Hungary	6000
352	Fovarosi Onkormanyzat Szent Margit Korhaza	Budapest		Hungary	1032
353	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest		Hungary	1062
354	Szent Imre Egyetemi Oktatokorhaz	Budapest		Hungary	1115
355	Semmelweis Egyetem III. sz Belgyogyaszati Klinika	Budapest		Hungary	1125
356	Fovarosi Onkormanyzat Uzsoki utcai Korhaz	Budapest		Hungary	1145
357	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz	Szolnok		Hungary	5000
358	MNJ Institute of Oncology	Hyderabad	Andhra Pradesh	India	500004
359	Dr. B. L. Kapur Memorial Hospital	New Delhi	Delhi	India	110005
360	HCG Cancer Centre	Vadodara	Gujarat	India	390012
361	Artemis Hospital	Gurgaon	Haryana	India	122001
362	Manipal Hospital	Bangalore	Karmnataka	India	560017
363	Regional Cancer Centre	Trivandrum	Kerala	India	695 011
364	Tata Memorial Hospital	Mumbai	Maharashtra	India	400012
365	HCG Manavata Cancer Centre	Nasik	Maharashtra	India	422001
366	Ruby Hall Clinic and Grant Medical Foundation	Pune	Maharashtra	India	411001
367	Deenanth Mangeshkar Hospital and Research Centre	Pune	Maharashtra	India	411004
368	Apollo Speciality Hospital	Chennai	Tamil Nadu	India	600018
369	Apollo Gleneagles Hospitals	Kolkata	West Bengal	India	700054
370	Medica Superspecialty Hospital	Kolkata	West Bengal	India	700099
371	HCG Cancer Centre	Ahmedabad		India	380060
372	Post Graduate Institute of Medical Education & Research	Chandigarh		India	160012
373	Soroka Medical Center	Beer Sheva		Israel	8410101
374	Rambam Medical Center	Haifa		Israel	3109601
375	Shaare Zedek Medical Center	Jerusalem		Israel	9103102
376	Hadassah Medical Center	Jerusalem		Israel	9112001
377	Meir Medical Center	Kfar Saba		Israel	4428164
378	Rabin Medical Center	Petach Tikva		Israel	4941492
379	Sheba Medical Center	Ramat Gan		Israel	5262000
380	Kaplan Medical Center	Rehovot		Israel	7610001
381	Assaf Harofeh Medical Center	Zerifin 70300		Israel	6093000
382	Ospedale Perrino	Brindisi	BR	Italy	72100
383	Azienda Ospedaliero Universitaria di Ferrara	Cona	Ferrara	Italy	44124
384	Istituto Scientifico Romagnolo - Studio e la Cura dei Tumori	Meldola	Forli	Italy	47014
385	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
386	Istituto Tumori Fondazione G. Pascale IRCCS	Napoli	Naples	Italy	80131
387	Azienda Ospedaliera Santa Maria	Terni	TR	Italy	05100
388	Ospedale Bellaria	Bologna		Italy	40139
389	Azienda Ospedaliera Universitaria Ospedale San Martino di Genova	Genova		Italy	16132
390	Ospedale Fatebenefratelli-Oftalmico	Milano		Italy	20121
391	ASST Monza - Presidio Ospedaliero di Monza	Milano		Italy	20900
392	Azienda Ospedaliera Universitaria Policlinico de Modena	Modena		Italy	41124
393	Azienda Ospedaliera Universitaria Federico II	Napoli		Italy	80131
394	Istituto Oncologico Veneto	Padova		Italy	35128
395	Azienda Ospedaliera Di Parma	Parma		Italy	43100
396	I.F.O. Istituto Nazionale Tumori Regina Elena	Roma		Italy	00144
397	Policlinico Ospedale S. Andrea	Roma		Italy	00189
398	Azienda Ospedaliero-Universitaria S.Giovanni Battista	Torino		Italy	10126
399	Presidio Ospedaliero Santa Chiara	Trento		Italy	38122
400	Aichi Cancer Center Hospital	Nagoya	Aichi	Japan	464-8681
401	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277 8577
402	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime	Japan	791-0280
403	JCHO Kurume General Hosp	Kurume	Fukuoka	Japan	830-0013
404	Gunma Prefectural Cancer Center	Ohta	Gunma	Japan	373-8550
405	Hiroshima University Hospital	Hiroshima-shi	Hiroshima-ken	Japan	734-8551
406	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido	Japan	003-0804
407	The Hospital of Hyogo College of Medecine	Nishinomiya	Hyogo	Japan	663-8501
408	University of tsukuba hospital	Tsukuba-shi	Ibaragi	Japan	305-8576
409	Tokai University Hospital	Isehara	Kanagawa	Japan	259-1193
410	St Marianna University School of Medicine Toyoko Hospital	Kawasaki	Kanagawa	Japan	216-8511
411	Kanagawa Cancer Center	Yokohama	Kanagawa	Japan	241 8515
412	KKR Tohoku Kosai Hospital	Aoba-ku, Sendai-shi	Miyagi	Japan	980-0803
413	Kindai University Hospital	Osaka Sayama-shi	Osaka	Japan	589 8511
414	Saitama Medical University International Medical Center	Hidaka	Saitama	Japan	350-1298
415	Saitama Cancer Center	Kitaadachi-Gun	Saitama	Japan	362-0806
416	Shizuoka Cancer Center	Sunto-Gun	Shizuoka	Japan	411-8777
417	Jichi Medical University Hospital	Shimotsuke	Tochigi	Japan	329-0498
418	Tochigi Cancer Center	Utsunomiya	Tochigi	Japan	320-0834
419	Juntendo University Hospital	Bunkyo-ku	Tokyo	Japan	113-8431
420	St. Lukes International Hospital	Chuo-Ku	Tokyo	Japan	104 8560
421	National Cancer Center Hospital	Chuo-Ku	Tokyo	Japan	104-0045
422	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo	Japan	135-8550
423	Showa University Hospital	Shinagawa-ku	Tokyo	Japan	142-8666
424	Tokyo Medical University Hospital	Shinjuku-ku	Tokyo	Japan	160-0023
425	National Center for Global Health and Medicine	Shinjuku-ku	Tokyo	Japan	162-8655
426	Chiba Cancer Center	Chiba		Japan	260-8717
427	Kyushu Cancer Center	Fukuoka		Japan	811-1395
428	Sagara Hospital	Kagoshima		Japan	892-0833
429	Kumamoto University Hospital	Kumamoto		Japan	860-8556
430	Kumamoto Shinto General hospital	Kumamoto		Japan	862-8655
431	Kyoto University Hospital	Kyoto		Japan	606-8507
432	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
433	National Hospital Organization Osaka National Hospital	Osaka		Japan	540-0006
434	Osaka International Cancer Institute	Osaka		Japan	541-8567
435	Chungbuk National University Hospital	Cheong Ju-City	Chung Cheong Buk-Do	Korea, Republic of	28644
436	Soonchunhyang University Hospital Cheonan	Cheonan	Chungcheongnam-do	Korea, Republic of	31151
437	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
438	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do	Korea, Republic of	13620
439	Dongnam Institute of Radiological and Medical Sciences	Busan	Gyeongsangnam Do	Korea, Republic of	46033
440	Gachon University Gil Medical Center	Incheon	Korea	Korea, Republic of	21565
441	Samsung Medical Center	Seoul	Korea	Korea, Republic of	06351
442	Korea University Guro Hospital	Seoul	Korea	Korea, Republic of	08308
443	Asan Medical Center	Songpa-gu	Seoul	Korea, Republic of	05505
444	Ewha University Mokdong Hospital	Seoul	Yangcheon-gu	Korea, Republic of	07985
445	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
446	Kyungpook National University Medical Center Chilgok Hospital	Daegu		Korea, Republic of	41404
447	Inha University Hospital	Incheon		Korea, Republic of	22332
448	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
449	Seoul National University Hospital	Seoul		Korea, Republic of	03080
450	Severance Hospital Yonsei University Health System	Seoul		Korea, Republic of	03722
451	Centro de Estudios y Prevencion del Cancer A.C.	Tuxtla Gutiérrez	Chiapas	Mexico	29038
452	CIMAB S.A. de C.V.	Torreon	Coahuila	Mexico	27000
453	Grupo Medico Camino S.C.	México City	Distrito Federal	Mexico	03310
454	Health Pharma Professional Research, S.A. de C.V.	Mexico City	Federal District	Mexico	03810
455	COI Centro Oncológico Internacional S.A.P.I de C.V.	Mexico	Federal District	Mexico	04700
456	Hospital Civil De Guadalajara Fray Antonio Alcalde	Guadalajara	Jalisco	Mexico	44280
457	COI Centro Oncológico Internacional S.A.P.I de C.V.	Tlajomulco de Zuniga	Jalisco	Mexico	45640
458	CRI Centro Regiomontano de Investigacion S.C.	Monterrey	Nuevo Leon	Mexico	64060
459	Christus Muguerza Clinica Vidriera	Monterrey	Nuevo Leon	Mexico	64570
460	Joaquin Gabriel Reinoso Toledo (Consultorios de Medicina Especializada)	Monterrey	Nuevo León	Mexico	64320
461	Neurociencias Estudios Clinicos S.C.	Culiacan	Sinaloa	Mexico	80020
462	Consultorio Centro Hemato Oncologico Privado	San Bernardino	Toluca	Mexico	50080
463	Medical Care and Research, S.A. de C.V.	Merida	Yucatan	Mexico	97070
464	Centro de Atención e Investigación Clínica en Oncología	Merida	Yucatan	Mexico	97138
465	Unidad de Investigacion en Salud de Chihuahua S.C.	Chihuahua		Mexico	31203
466	Oaxaca Site Management Organization SC	Oaxaca		Mexico	68000
467	Oncológica de Puebla	Puebla		Mexico	72530
468	Oncológico Potosino	San Luis Potosí		Mexico	78250
469	Onze Lieve Vrouwe Gasthuis (OLVG)	Amsterdam		Netherlands	1091AC
470	HagaZiekenhuis	Den Haag		Netherlands	2545 AA
471	Albert Schweitzer Ziekenhuis	Dordrecht		Netherlands	3318 AT
472	Universitair Medisch Centrum Maastricht	Maastricht		Netherlands	6229 HX
473	Palmerston North Hospital	Palmerston North	Wanganui	New Zealand	4414
474	Auckland City Hospital	Auckland		New Zealand	1023
475	Waikato Hospital	Hamilton		New Zealand	3204
476	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
477	Szpital Morski im. PCK Sp. z o.o.	Gdynia		Poland	81-519
478	Przychodnia Lekarska "Komed"	Konin		Poland	62-500
479	Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.	Lodz		Poland	90-242
480	Centrum Onkologii Ziemii Lubelskiej im. sw. Jana z Dukli	Lublin		Poland	20-090
481	Olsztynski Osrodek Onkologiczny	Olsztyn		Poland	10-513
482	Opolskie Centrum Onkologii	Opole		Poland	45-060
483	Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie	Poznan		Poland	61-866
484	MAGODENT Szpital Onkologiczny Elblaska	Warszawa		Poland	01-748
485	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut	Warszawa		Poland	02-781
486	Dolnoslaskie Centrum Onkologii	Wroclaw		Poland	53-413
487	Instituto Português de Oncologia Dr. Francisco Gentil	Coimbra		Portugal	3000-075
488	Fundação Champalimaud	Lisboa		Portugal	1400-038
489	Centro Hospitalar Lisboa Norte - Hospital de Santa Maria	Lisboa		Portugal	1649-035
490	Hospital Geral de Santo Antonio	Porto		Portugal	4099-001
491	IPOFG - Porto	Porto		Portugal	4200-072
492	Puerto Rico Hematology/Oncology Group	Bayamon		Puerto Rico	00961
493	University Of Puerto Rico	San Juan		Puerto Rico	00935
494	Centrul de Oncologie Sf. Nectarie SRL	Craiova	Dolj	Romania	200347
495	S.C. R.T.C. Radiology Therapeutic Center S.R.L.	Otopeni	Ilfov	Romania	075100
496	SC Oncopremium Team SRL	Baia Mare	Maramureș	Romania	430291
497	Institutul Oncologic Dr Trestioreanu Bucuresti	Bucuresti	Sector 2	Romania	022328
498	Spitalul Clinic Filantropia	Bucuresti		Romania	011171
499	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca	Cluj-Napoca		Romania	400015
500	Spitalul Clinic Judetean de Urgenta Sf.Apostol Andrei Constanta	Constanta		Romania	900591
501	Kazan Oncology Dispensary	Kazan	Tatarstan Republic	Russian Federation	420029
502	Chelyabinsk Regional Oncology Dispensary	Chelyabinsk		Russian Federation	454087
503	SHI Kaluga Regional Hospital	Kaluga		Russian Federation	248007
504	Kursk Regional Oncology Dispensary	Kursk		Russian Federation	305035
505	Leningrad Regional Oncology Dispensary	Leningrad Region		Russian Federation	188663
506	Principal Military Clinical Hospital n.a. N. N. Burdenko	Moscow		Russian Federation	105229
507	Blokhin Cancer Research Center	Moscow		Russian Federation	115478
508	Russian Oncological Research Center	Moscow		Russian Federation	115478
509	Orenburg Regional Clinical Oncology Dispensary	Orenburg		Russian Federation	460021
510	St. Petersburg City Clinical Oncological Dispensary	Saint-Petersburg		Russian Federation	198255
511	Samara Regional Clinical Oncology Dispensary	Samara		Russian Federation	443031
512	GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen of Health	St. Petersburg		Russian Federation	195067
513	FGU Research Institution of Oncology	St. Petersburg		Russian Federation	197758
514	St-Petersburg scientifical practical cente spec medical care	St. Petersburg		Russian Federation	197758
515	Volgograd regional clinical oncology dispensary	Volgograd		Russian Federation	400138
516	Yaroslavl region regional clinical oncology hospital	Yaroslavl		Russian Federation	150054
517	King Fahad Specialist Hospital-Dammam	Dammam		Saudi Arabia	31444
518	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia	11211
519	King Abdulaziz Medical City - National Guard Hospital	Riyadh		Saudi Arabia	11426
520	King Fahad Medical City	Riyadh		Saudi Arabia	11525
521	National Cancer Center	Singapore		Singapore	169610
522	National University Hospital	Singapore		Singapore	669606
523	Eastleigh Breast Care Center	Pretoria	Gauteng	South Africa	0081
524	Cancercare Rondebosch Oncology	Cape Town		South Africa	7700
525	Cancercare	George		South Africa	6530
526	Sandton Oncology Centre	Johannesburg		South Africa	2196
527	Langenhoven Drive Oncology Centre	Port Elizabeth		South Africa	6045
528	Mary Potter Oncology Center	Pretoria		South Africa	0181
529	Hospital Clinico Universitario Virgen de la Victoria	Malaga	Andalucia	Spain	29010
530	Hospital Universitario Virgen del Rocio	Sevilla	Andalucía	Spain	41013
531	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain	33011
532	Hospital Universitari Arnau de Vilanova	Lleida	Cataluña	Spain	25198
533	Hospital Clinico Universitario de Santiago	Santiago de Compostela	La Coruna	Spain	15706
534	Hospital Fundación Alcorcón	Alcorcón	Madrid	Spain	28922
535	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid	Spain	28223
536	Hospital Universitario de Canarias	La Laguna	Santa Cruz De Tenerife	Spain	38320
537	Hospital del Mar	Barcelona		Spain	08003
538	Hospital Quirón Salud Barcelona-Instituto Oncológico Baselga	Barcelona		Spain	08023
539	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
540	Hospital Clinic I Provincial	Barcelona		Spain	08036
541	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
542	Hospital Reina Sofia	Cordoba		Spain	14004
543	Hospital Clinico Universitario San Cecilio	Granada		Spain	18016
544	Complejo Hospitalario Ciudad De Jaen	Jaen		Spain	23007
545	Hospital De La Princesa	Madrid		Spain	28006
546	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
547	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
548	Hospital Clinico San Carlos	Madrid		Spain	28040
549	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
550	Hospital Madrid Norte Sanchinarro	Madrid		Spain	28050
551	Hospital Clinico De Salamanca	Salamanca		Spain	37007
552	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
553	Hospital Universitario Nuestra Señora de Valme	Sevilla		Spain	41014
554	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
555	Hospital Quirón Salud Valencia	Valencia		Spain	46010
556	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
557	Norrlands universitetssjukhus	Umeå	Vasterbotten	Sweden	90185
558	Skånes universitetssjukhus Lund	Lund		Sweden	22185
559	Länssjukhuset Sundsvall	Sundsvall		Sweden	85186
560	Västmanlands sjukhus Västerås	Västerås		Sweden	SE-72189
561	Växjö Centrallasarettet	Växjö		Sweden	35234
562	Changhua Christian Hospital	Changhua		Taiwan	500
563	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City		Taiwan	80756
564	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung		Taiwan	83301
565	Tri-Service General Hospital	Neihu Taipei		Taiwan	11490
566	Taipei Medical University- Shuang Ho Hospital	New Taipei City		Taiwan	235
567	China Medical University Hospital	Taichung City		Taiwan	40447
568	MacKay Memorial Hospital	Taipei City		Taiwan	10449
569	National Taiwan University Hospital	Taipei		Taiwan	10002
570	Taipei Veterans General Hospital	Taipei		Taiwan	11217
571	Sun Yat-Sen Cancer Center	Taipei		Taiwan	112
572	Chang Gung Memorial Hospital - Linkou	Taoyuan City		Taiwan	33305
573	Ankara Gulhane Training ve Research Hospital	Ankara	Kecioren	Turkey	06010
574	Baskent Adana Educational Hospital	Adana		Turkey	1250
575	Ankara University Medicine Hospital	Ankara		Turkey	06100
576	Hacettepe University Faculty of Medicine	Ankara		Turkey	06100
577	Dr.Abdurrahman Yurtaslan Ankara Oncology Training & Res Hosp	Ankara		Turkey	06200
578	Akdeniz University Medical Faculty	Antalya		Turkey	07059
579	Trakya University Faculty of Medicine	Edirne		Turkey	22030
580	Istanbul University	Istanbul		Turkey	34098
581	Acibadem Altunizade Hastanesi	Istanbul		Turkey	34662
582	Istanbul Medeniyet University Medical Faculty	Istanbul		Turkey	34722
583	Ege University Faculty of Medicine	Izmir		Turkey	35100
584	Medical Park Izmir Hospital	Izmir		Turkey	35575
585	Kocaeli University Medical Faculty Hospital	Izmit		Turkey	41380
586	Inonu University Medical Faculty	Malatya		Turkey	44280
587	Dnipropetrovsk City Multifunctional Clinical Hospital #4 of Dnipropetrovsk Regional Council	Dnipro		Ukraine	49102
588	Commu Instit "Krivorizhskiy oncology dispensary" Dnip reg Co	Kriviy Rig		Ukraine	50048
589	Communal Enterprise "Volyn Regional Medical Oncology Center"	Lutsk		Ukraine	43018
590	Odesa Regional Clinical Hospital	Odesa		Ukraine	65117
591	Poltava Regional Clinical Oncological Dispensary	Poltava		Ukraine	36011
592	Central Municipal Clinical Hospital	Uzhhorod		Ukraine	88000
593	Podilskyi Regional Center of Oncology	Vinnytsia		Ukraine	21029
594	University Hospital of North Tees	Stockton-on-Tees	Cleveland	United Kingdom	TS19 8PE
595	Royal Cornwall Hospital	Truro	Cornwall	United Kingdom	TR1 3LJ
596	Broomfield Hospital	Chelmsford	Essex	United Kingdom	CM2 5ET
597	North Middlesex Hospital	London	Greater London	United Kingdom	N18 1QX
598	Christie NHS Foundation Trust	Manchester	Greater Manchester	United Kingdom	M20 4QL
599	Victoria Hospital	Blackpool	Lancashire	United Kingdom	FY3 8NR
600	Royal Preston Hospital	Preston	Lancashire	United Kingdom	PR2 9HT
601	Charing Cross Hospital	Chelsea	London	United Kingdom	W6 8RF
602	Mount Vernon Hospital	Northwood	Middlesex	United Kingdom	HA6 2RN
603	Nottingham City Hospital	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
604	Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
605	Musgrove Park Hospital	Taunton	Somerset	United Kingdom	TA1 5DA
606	Royal Surrey County Hospital	Guildford	Surrey	United Kingdom	GU2 7XX
607	Guys/St. Thomas Hospital	London	Surrey	United Kingdom	SE1 9RT
608	Sarah Canon Research Institute UK	London	Surrey	United Kingdom	W1G 6AD
609	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
610	Airedale General Hospital	Keighley	WEST Yorkshire	United Kingdom	BD20 6TD
611	Pilgrim Hospital	Boston		United Kingdom	PE21 9QS
612	Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Eli Lilly and Company
• NSABP Foundation Inc

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 - Sep 18, 2019
• Statistical Analysis Plan - Jun 5, 2020

More Information

Additional Information:

• A Study to Compare Treatment After Surgery of Abemaciclib (LY2835219) Combined With Standard Endocrine Therapy Versus Endocrine Therapy Alone in Participants With Breast Cancer (monarchE)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03155997
• Other Study ID Numbers: 16338; I3Y-MC-JPCF; 2016-004362-26; NSABP B-58
• First Posted: May 16, 2017
• Last Update Posted: Jan 24, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: early stage breast cancer; cyclin-dependent kinase (CDK)
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	Completers included participants who had recurrence disease, death due to any cause, and participants off treatment but on study follow-up.

Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy	Endocrine Therapy
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
Period Title: Overall Study
STARTED	2808	2829
Received at Least One Dose of Study Drug	2791	2800
COMPLETED	650	607
NOT COMPLETED	2158	2222

Baseline Characteristics

Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy	Endocrine Therapy	Total
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Total of all reporting groups
Overall Participants	2808	2829	5637
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.20 (11.26)	52.10 (11.20)	52.10 (11.23)
Sex: Female, Male (Count of Participants)
Female	2787 99.3%	2814 99.5%	5601 99.4%
Male	21 0.7%	15 0.5%	36 0.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	355 12.6%	378 13.4%	733 13%
Not Hispanic or Latino	1734 61.8%	1738 61.4%	3472 61.6%
Unknown or Not Reported	719 25.6%	713 25.2%	1432 25.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	64 2.3%	58 2.1%	122 2.2%
Asian	675 24%	669 23.6%	1344 23.8%
Native Hawaiian or Other Pacific Islander	3 0.1%	4 0.1%	7 0.1%
Black or African American	57 2%	53 1.9%	110 2%
White	1947 69.3%	1978 69.9%	3925 69.6%
More than one race	22 0.8%	25 0.9%	47 0.8%
Unknown or Not Reported	40 1.4%	42 1.5%	82 1.5%
Region of Enrollment (Count of Participants)
Argentina	77 2.7%	68 2.4%	145 2.6%
Australia	108 3.8%	109 3.9%	217 3.8%
Austria	22 0.8%	20 0.7%	42 0.7%
Belgium	65 2.3%	51 1.8%	116 2.1%
Brazil	144 5.1%	153 5.4%	297 5.3%
Canada	28 1%	16 0.6%	44 0.8%
China	187 6.7%	170 6%	357 6.3%
Czechia	15 0.5%	12 0.4%	27 0.5%
Denmark	54 1.9%	58 2.1%	112 2%
Finland	45 1.6%	49 1.7%	94 1.7%
France	86 3.1%	101 3.6%	187 3.3%
Germany	148 5.3%	152 5.4%	300 5.3%
Greece	74 2.6%	64 2.3%	138 2.4%
Hong Kong	8 0.3%	12 0.4%	20 0.4%
Hungary	24 0.9%	28 1%	52 0.9%
India	59 2.1%	53 1.9%	112 2%
Israel	39 1.4%	38 1.3%	77 1.4%
Italy	72 2.6%	59 2.1%	131 2.3%
Japan	181 6.4%	196 6.9%	377 6.7%
Mexico	104 3.7%	121 4.3%	225 4%
Netherlands	5 0.2%	14 0.5%	19 0.3%
New Zealand	21 0.7%	22 0.8%	43 0.8%
Poland	65 2.3%	60 2.1%	125 2.2%
Portugal	21 0.7%	16 0.6%	37 0.7%
Puerto Rico	1 0%	3 0.1%	4 0.1%
Romania	53 1.9%	60 2.1%	113 2%
Russia	66 2.4%	73 2.6%	139 2.5%
Saudi Arabia	5 0.2%	9 0.3%	14 0.2%
Singapore	11 0.4%	21 0.7%	32 0.6%
South Africa	3 0.1%	6 0.2%	9 0.2%
South Korea	122 4.3%	123 4.3%	245 4.3%
Spain	144 5.1%	148 5.2%	292 5.2%
Sweden	7 0.2%	5 0.2%	12 0.2%
Taiwan	64 2.3%	60 2.1%	124 2.2%
Turkey	125 4.5%	110 3.9%	235 4.2%
Ukraine	54 1.9%	51 1.8%	105 1.9%
United Kingdom	99 3.5%	100 3.5%	199 3.5%
United States	402 14.3%	418 14.8%	820 14.5%

Outcome Measures

1. Primary Outcome

Title	Invasive Disease Free Survival (IDFS)
Description	IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause.
Time Frame	Baseline to Recurrence or Death from Any Cause (Up to 32 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants (including the censored participants). 2672 participants were censored in "150 mg Abemaciclib + Endocrine Therapy," 2642 participants were censored in "Endocrine Therapy."

Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy	Endocrine Therapy
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
Measure Participants	2808	2829
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	150 mg Abemaciclib + Endocrine Therapy, Endocrine Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.00957
	Comments
	Method	Log Rank
	Comments	Stratified by Interactive Web Response Systems (IWRS) Geographical Region, IWRS Prior Treatment, IWRS Menopausal Status
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.747
	Confidence Interval	(2-Sided) 95%; 0.598 to 0.932
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified by IWRS Geographical Region, IWRS Prior Treatment, IWRS Menopausal Status

2. Secondary Outcome

Title	IDFS for Participants With Ki-67 Index ≥20%
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Distant Relapse-Free Survival (DRFS)
Description	Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first.
Time Frame	Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)

Outcome Measure Data

Analysis Population Description

All randomized participants (including the censored participants). 2702 participants were censored in "150 mg Abemaciclib + Endocrine Therapy," 2677 participants were censored in "Endocrine Therapy."

Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy	Endocrine Therapy
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.	Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
Measure Participants	2808	2829
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	150 mg Abemaciclib + Endocrine Therapy, Endocrine Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.717
	Confidence Interval	(2-Sided) 95%; 0.559 to 0.920
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified by IWRS Geographical Region, IWRS Prior Treatment, IWRS Menopausal Status

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline to Death from Any Cause (Approximately 10 Years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
Description	Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib
Time Frame	Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of Abemaciclib and had evaluable PK data.

Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
Measure Participants	483
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter (ng/mL)]	143 (110)

6. Secondary Outcome

Title	Change From Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B)
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline, Follow Up (Approximately 3 Years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change From Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline, Follow Up (Approximately 3 Years)]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change From Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline, Follow Up (Approximately 3 Years)]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change From Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
Description	Outcome data will be provided after the study is completed.
Time Frame	Baseline, Follow Up (Approximately 3 Years)]

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Baseline to 32 Months
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Arm/Group Title	150 mg Abemaciclib + Endocrine Therapy		Endocrine Therapy
Arm/Group Description	Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.		Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.
All Cause Mortality
	150 mg Abemaciclib + Endocrine Therapy		Endocrine Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/2791 (1.4%)		36/2800 (1.3%)
Serious Adverse Events
	150 mg Abemaciclib + Endocrine Therapy		Endocrine Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	344/2791 (12.3%)		202/2800 (7.2%)
Blood and lymphatic system disorders
Anaemia	8/2791 (0.3%)	8	2/2800 (0.1%)	2
Bone marrow oedema	1/2791 (0%)	1	0/2800 (0%)	0
Disseminated intravascular coagulation	1/2791 (0%)	1	0/2800 (0%)	0
Febrile neutropenia	4/2791 (0.1%)	4	0/2800 (0%)	0
Leukopenia	4/2791 (0.1%)	4	0/2800 (0%)	0
Lymphadenopathy mediastinal	0/2791 (0%)	0	1/2800 (0%)	1
Neutropenia	3/2791 (0.1%)	3	1/2800 (0%)	1
Pancytopenia	1/2791 (0%)	1	0/2800 (0%)	0
Thrombocytopenia	4/2791 (0.1%)	5	1/2800 (0%)	1
Cardiac disorders
Acute left ventricular failure	1/2791 (0%)	1	0/2800 (0%)	0
Angina pectoris	1/2791 (0%)	1	0/2800 (0%)	0
Atrial fibrillation	6/2791 (0.2%)	6	1/2800 (0%)	1
Atrioventricular block complete	0/2791 (0%)	0	1/2800 (0%)	1
Cardiac arrest	2/2791 (0.1%)	2	0/2800 (0%)	0
Cardiac failure	4/2791 (0.1%)	5	1/2800 (0%)	1
Cardiotoxicity	0/2791 (0%)	0	1/2800 (0%)	1
Coronary artery disease	1/2791 (0%)	1	1/2800 (0%)	1
Myocardial infarction	4/2791 (0.1%)	4	1/2800 (0%)	1
Myocardial ischaemia	1/2791 (0%)	1	0/2800 (0%)	0
Pericarditis	0/2791 (0%)	0	1/2800 (0%)	1
Sinus tachycardia	1/2791 (0%)	1	1/2800 (0%)	1
Stress cardiomyopathy	0/2791 (0%)	0	2/2800 (0.1%)	2
Supraventricular tachycardia	1/2791 (0%)	1	1/2800 (0%)	1
Ventricular fibrillation	1/2791 (0%)	1	0/2800 (0%)	0
Ear and labyrinth disorders
Tympanic membrane perforation	0/2791 (0%)	0	1/2800 (0%)	1
Vertigo	0/2791 (0%)	0	1/2800 (0%)	1
Eye disorders
Angle closure glaucoma	1/2791 (0%)	1	0/2800 (0%)	0
Cataract	0/2791 (0%)	0	1/2800 (0%)	1
Eyelid ptosis	1/2791 (0%)	1	0/2800 (0%)	0
Macular hole	1/2791 (0%)	1	0/2800 (0%)	0
Macular pseudohole	0/2791 (0%)	0	1/2800 (0%)	1
Retinal detachment	2/2791 (0.1%)	2	0/2800 (0%)	0
Gastrointestinal disorders
Abdominal pain	6/2791 (0.2%)	6	1/2800 (0%)	1
Anal fissure	1/2791 (0%)	1	0/2800 (0%)	0
Anal fistula	1/2791 (0%)	1	0/2800 (0%)	0
Chronic gastritis	0/2791 (0%)	0	1/2800 (0%)	1
Colitis	3/2791 (0.1%)	3	3/2800 (0.1%)	3
Colitis ischaemic	1/2791 (0%)	1	0/2800 (0%)	0
Dental caries	1/2791 (0%)	1	0/2800 (0%)	0
Diarrhoea	15/2791 (0.5%)	18	0/2800 (0%)	0
Enteritis	1/2791 (0%)	1	0/2800 (0%)	0
Food poisoning	2/2791 (0.1%)	2	0/2800 (0%)	0
Gastritis	1/2791 (0%)	1	1/2800 (0%)	1
Gastritis erosive	1/2791 (0%)	1	0/2800 (0%)	0
Gastrointestinal fistula	1/2791 (0%)	1	0/2800 (0%)	0
Gastrointestinal haemorrhage	1/2791 (0%)	1	2/2800 (0.1%)	2
Haemorrhoidal haemorrhage	1/2791 (0%)	1	0/2800 (0%)	0
Haemorrhoids	1/2791 (0%)	1	0/2800 (0%)	0
Inguinal hernia	0/2791 (0%)	0	1/2800 (0%)	1
Intestinal obstruction	3/2791 (0.1%)	3	2/2800 (0.1%)	2
Large intestine polyp	0/2791 (0%)	0	1/2800 (0%)	1
Nausea	3/2791 (0.1%)	4	1/2800 (0%)	1
Oesophagitis	0/2791 (0%)	0	1/2800 (0%)	1
Pancreatitis	6/2791 (0.2%)	6	2/2800 (0.1%)	2
Pancreatitis acute	2/2791 (0.1%)	2	0/2800 (0%)	0
Peritoneal adhesions	0/2791 (0%)	0	1/2800 (0%)	1
Stomatitis	2/2791 (0.1%)	2	0/2800 (0%)	0
Umbilical hernia	0/2791 (0%)	0	1/2800 (0%)	1
Vomiting	3/2791 (0.1%)	3	0/2800 (0%)	0
General disorders
Capsular contracture associated with breast implant	2/2791 (0.1%)	2	1/2800 (0%)	2
Chest pain	4/2791 (0.1%)	4	1/2800 (0%)	1
Fatigue	2/2791 (0.1%)	2	0/2800 (0%)	0
General physical health deterioration	4/2791 (0.1%)	4	0/2800 (0%)	0
Hyperplasia	0/2791 (0%)	0	1/2800 (0%)	1
Impaired healing	2/2791 (0.1%)	2	3/2800 (0.1%)	3
Inflammation	0/2791 (0%)	0	1/2800 (0%)	1
Non-cardiac chest pain	1/2791 (0%)	1	2/2800 (0.1%)	2
Pain	1/2791 (0%)	1	0/2800 (0%)	0
Pyrexia	7/2791 (0.3%)	7	0/2800 (0%)	0
Sudden death	0/2791 (0%)	0	1/2800 (0%)	1
Hepatobiliary disorders
Biliary colic	1/2791 (0%)	1	0/2800 (0%)	0
Cholecystitis	10/2791 (0.4%)	10	2/2800 (0.1%)	2
Cholecystitis acute	2/2791 (0.1%)	2	0/2800 (0%)	0
Cholelithiasis	2/2791 (0.1%)	2	3/2800 (0.1%)	3
Drug-induced liver injury	1/2791 (0%)	1	0/2800 (0%)	0
Hepatic cirrhosis	1/2791 (0%)	1	0/2800 (0%)	0
Hepatic function abnormal	2/2791 (0.1%)	2	1/2800 (0%)	1
Jaundice	0/2791 (0%)	0	1/2800 (0%)	1
Immune system disorders
Anaphylactic reaction	1/2791 (0%)	1	1/2800 (0%)	1
Drug hypersensitivity	1/2791 (0%)	1	0/2800 (0%)	0
Infections and infestations
Abdominal infection	0/2791 (0%)	0	1/2800 (0%)	1
Abscess	1/2791 (0%)	1	0/2800 (0%)	0
Anal abscess	1/2791 (0%)	1	0/2800 (0%)	0
Appendicitis	3/2791 (0.1%)	3	2/2800 (0.1%)	2
Appendicitis perforated	1/2791 (0%)	1	0/2800 (0%)	0
Bacteraemia	2/2791 (0.1%)	2	1/2800 (0%)	1
Biliary tract infection	1/2791 (0%)	1	0/2800 (0%)	0
Breast abscess	3/2791 (0.1%)	3	1/2800 (0%)	1
Breast cellulitis	5/2791 (0.2%)	5	4/2800 (0.1%)	4
Bronchitis	0/2791 (0%)	0	1/2800 (0%)	1
Campylobacter gastroenteritis	1/2791 (0%)	1	0/2800 (0%)	0
Cellulitis	11/2791 (0.4%)	13	9/2800 (0.3%)	9
Cellulitis staphylococcal	1/2791 (0%)	1	0/2800 (0%)	0
Clostridium colitis	1/2791 (0%)	1	0/2800 (0%)	0
Clostridium difficile colitis	1/2791 (0%)	1	0/2800 (0%)	0
Coronavirus infection	1/2791 (0%)	1	0/2800 (0%)	0
Device related infection	0/2791 (0%)	0	2/2800 (0.1%)	2
Diverticulitis	3/2791 (0.1%)	4	5/2800 (0.2%)	5
Ear infection	0/2791 (0%)	0	1/2800 (0%)	1
Erysipelas	5/2791 (0.2%)	9	0/2800 (0%)	0
Escherichia pyelonephritis	0/2791 (0%)	0	1/2800 (0%)	1
Febrile infection	1/2791 (0%)	1	0/2800 (0%)	0
Gastroenteritis	1/2791 (0%)	1	0/2800 (0%)	0
Gastroenteritis clostridial	1/2791 (0%)	1	0/2800 (0%)	0
Hepatitis e	1/2791 (0%)	1	0/2800 (0%)	0
Implant site infection	1/2791 (0%)	1	0/2800 (0%)	0
Infection	0/2791 (0%)	0	1/2800 (0%)	1
Infective pulmonary exacerbation of cystic fibrosis	0/2791 (0%)	0	1/2800 (0%)	1
Influenza	7/2791 (0.3%)	7	3/2800 (0.1%)	3
Intervertebral discitis	0/2791 (0%)	0	1/2800 (0%)	1
Laryngitis	1/2791 (0%)	1	0/2800 (0%)	0
Lower respiratory tract infection	1/2791 (0%)	1	1/2800 (0%)	1
Lymphangitis	2/2791 (0.1%)	2	0/2800 (0%)	0
Mastitis	3/2791 (0.1%)	4	5/2800 (0.2%)	5
Mastoiditis	1/2791 (0%)	1	0/2800 (0%)	0
Meningitis viral	1/2791 (0%)	1	0/2800 (0%)	0
Nasopharyngitis	1/2791 (0%)	1	0/2800 (0%)	0
Neutropenic infection	1/2791 (0%)	1	0/2800 (0%)	0
Osteomyelitis	0/2791 (0%)	0	1/2800 (0%)	1
Peritonitis	0/2791 (0%)	0	1/2800 (0%)	1
Pneumonia	23/2791 (0.8%)	23	14/2800 (0.5%)	15
Pneumonia bacterial	1/2791 (0%)	1	1/2800 (0%)	1
Pneumonia influenzal	1/2791 (0%)	1	0/2800 (0%)	0
Pneumonia streptococcal	1/2791 (0%)	1	0/2800 (0%)	0
Post procedural cellulitis	1/2791 (0%)	1	1/2800 (0%)	1
Post procedural infection	1/2791 (0%)	1	0/2800 (0%)	0
Postoperative wound infection	2/2791 (0.1%)	2	1/2800 (0%)	1
Pyelonephritis	2/2791 (0.1%)	2	2/2800 (0.1%)	2
Respiratory tract infection	0/2791 (0%)	0	1/2800 (0%)	2
Sepsis	5/2791 (0.2%)	5	2/2800 (0.1%)	2
Septic shock	0/2791 (0%)	0	1/2800 (0%)	1
Skin infection	0/2791 (0%)	0	1/2800 (0%)	1
Soft tissue infection	1/2791 (0%)	1	0/2800 (0%)	0
Tuberculosis	1/2791 (0%)	1	0/2800 (0%)	0
Upper respiratory tract infection	6/2791 (0.2%)	6	0/2800 (0%)	0
Urinary tract infection	12/2791 (0.4%)	12	4/2800 (0.1%)	4
Urosepsis	0/2791 (0%)	0	1/2800 (0%)	1
Viral infection	2/2791 (0.1%)	2	0/2800 (0%)	0
Wound infection	2/2791 (0.1%)	2	0/2800 (0%)	0
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/2791 (0%)	1	0/2800 (0%)	0
Alcohol poisoning	1/2791 (0%)	1	0/2800 (0%)	0
Ankle fracture	0/2791 (0%)	0	3/2800 (0.1%)	3
Breast procedural complication	2/2791 (0.1%)	2	0/2800 (0%)	0
Clavicle fracture	1/2791 (0%)	1	0/2800 (0%)	0
Exposure during pregnancy	1/2791 (0%)	1	0/2800 (0%)	0
Fall	1/2791 (0%)	1	1/2800 (0%)	1
Femoral neck fracture	0/2791 (0%)	0	1/2800 (0%)	1
Foot fracture	1/2791 (0%)	1	0/2800 (0%)	0
Fracture	1/2791 (0%)	1	0/2800 (0%)	0
Hip fracture	1/2791 (0%)	1	2/2800 (0.1%)	3
Humerus fracture	0/2791 (0%)	0	2/2800 (0.1%)	2
Incisional hernia	1/2791 (0%)	1	0/2800 (0%)	0
Jaw fracture	1/2791 (0%)	1	0/2800 (0%)	0
Joint injury	1/2791 (0%)	1	0/2800 (0%)	0
Ligament rupture	1/2791 (0%)	1	0/2800 (0%)	0
Post procedural haematoma	1/2791 (0%)	1	0/2800 (0%)	0
Post procedural haemorrhage	0/2791 (0%)	0	1/2800 (0%)	1
Postoperative adhesion	1/2791 (0%)	1	0/2800 (0%)	0
Postoperative thoracic procedure complication	0/2791 (0%)	0	1/2800 (0%)	1
Postoperative wound complication	0/2791 (0%)	0	1/2800 (0%)	1
Procedural complication	1/2791 (0%)	1	0/2800 (0%)	0
Radiation pneumonitis	3/2791 (0.1%)	3	1/2800 (0%)	1
Radius fracture	1/2791 (0%)	1	1/2800 (0%)	1
Rib fracture	2/2791 (0.1%)	2	1/2800 (0%)	1
Skin flap necrosis	0/2791 (0%)	0	1/2800 (0%)	1
Spinal fracture	0/2791 (0%)	0	1/2800 (0%)	1
Thermal burn	1/2791 (0%)	1	0/2800 (0%)	0
Wound complication	0/2791 (0%)	0	1/2800 (0%)	1
Wound dehiscence	0/2791 (0%)	0	4/2800 (0.1%)	4
Wound necrosis	1/2791 (0%)	1	0/2800 (0%)	0
Wrist fracture	1/2791 (0%)	1	1/2800 (0%)	1
Investigations
Alanine aminotransferase increased	5/2791 (0.2%)	5	1/2800 (0%)	1
Aspartate aminotransferase increased	5/2791 (0.2%)	5	1/2800 (0%)	1
Blood creatinine increased	1/2791 (0%)	1	0/2800 (0%)	0
International normalised ratio increased	0/2791 (0%)	0	1/2800 (0%)	1
Occult blood	1/2791 (0%)	1	0/2800 (0%)	0
Transaminases increased	2/2791 (0.1%)	2	0/2800 (0%)	0
Metabolism and nutrition disorders
Dehydration	7/2791 (0.3%)	9	0/2800 (0%)	0
Food intolerance	1/2791 (0%)	1	0/2800 (0%)	0
Hypercalcaemia	0/2791 (0%)	0	1/2800 (0%)	1
Hyperglycaemia	1/2791 (0%)	1	2/2800 (0.1%)	2
Hypocalcaemia	0/2791 (0%)	0	1/2800 (0%)	1
Hypokalaemia	4/2791 (0.1%)	4	0/2800 (0%)	0
Hyponatraemia	1/2791 (0%)	1	2/2800 (0.1%)	2
Hypophosphataemia	1/2791 (0%)	1	0/2800 (0%)	0
Hypovolaemia	0/2791 (0%)	0	1/2800 (0%)	1
Metabolic acidosis	1/2791 (0%)	1	0/2800 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/2791 (0%)	1	0/2800 (0%)	0
Fistula	0/2791 (0%)	0	1/2800 (0%)	1
Flank pain	2/2791 (0.1%)	2	0/2800 (0%)	0
Intervertebral disc protrusion	1/2791 (0%)	1	3/2800 (0.1%)	3
Myositis	1/2791 (0%)	1	0/2800 (0%)	0
Neck pain	0/2791 (0%)	0	1/2800 (0%)	1
Osteoarthritis	0/2791 (0%)	0	2/2800 (0.1%)	2
Osteonecrosis	1/2791 (0%)	1	0/2800 (0%)	0
Rheumatoid arthritis	1/2791 (0%)	1	1/2800 (0%)	1
Rotator cuff syndrome	1/2791 (0%)	1	0/2800 (0%)	0
Spinal osteoarthritis	0/2791 (0%)	0	1/2800 (0%)	1
Tenosynovitis	0/2791 (0%)	0	1/2800 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	0/2791 (0%)	0	1/2800 (0%)	1
Cervix carcinoma	0/2770 (0%)	0	2/2785 (0.1%)	2
Colon cancer	1/2791 (0%)	1	0/2800 (0%)	0
Colorectal carcinoma stage 0	1/2791 (0%)	1	0/2800 (0%)	0
Endometrial neoplasm	0/2770 (0%)	0	1/2785 (0%)	1
Fibroadenoma of breast	1/2791 (0%)	1	0/2800 (0%)	0
Gastrointestinal adenocarcinoma	0/2791 (0%)	0	1/2800 (0%)	1
Malignant melanoma	1/2791 (0%)	1	0/2800 (0%)	0
Meningioma benign	1/2791 (0%)	1	0/2800 (0%)	0
Non-small cell lung cancer	1/2791 (0%)	1	0/2800 (0%)	0
Papillary thyroid cancer	0/2791 (0%)	0	1/2800 (0%)	1
Thyroid adenoma	0/2791 (0%)	0	1/2800 (0%)	1
Thyroid cancer	1/2791 (0%)	1	1/2800 (0%)	1
Tumour pain	1/2791 (0%)	1	0/2800 (0%)	0
Uterine leiomyoma	1/2770 (0%)	1	2/2785 (0.1%)	2
Nervous system disorders
Carotid artery aneurysm	0/2791 (0%)	0	1/2800 (0%)	1
Carpal tunnel syndrome	0/2791 (0%)	0	2/2800 (0.1%)	2
Cerebral haemorrhage	2/2791 (0.1%)	2	0/2800 (0%)	0
Cerebral infarction	2/2791 (0.1%)	2	0/2800 (0%)	0
Cerebral ischaemia	1/2791 (0%)	1	1/2800 (0%)	1
Cerebral venous thrombosis	2/2791 (0.1%)	2	0/2800 (0%)	0
Cerebrospinal fluid leakage	0/2791 (0%)	0	1/2800 (0%)	1
Cerebrovascular accident	1/2791 (0%)	1	1/2800 (0%)	1
Dizziness	0/2791 (0%)	0	1/2800 (0%)	1
Extrapyramidal disorder	1/2791 (0%)	1	0/2800 (0%)	0
Headache	1/2791 (0%)	1	0/2800 (0%)	0
Hemiparesis	1/2791 (0%)	1	0/2800 (0%)	0
Ischaemic stroke	3/2791 (0.1%)	3	1/2800 (0%)	1
Memory impairment	1/2791 (0%)	1	0/2800 (0%)	0
Monoparesis	0/2791 (0%)	0	1/2800 (0%)	1
Movement disorder	1/2791 (0%)	1	0/2800 (0%)	0
Nerve compression	1/2791 (0%)	1	0/2800 (0%)	0
Neuropathy	1/2791 (0%)	1	1/2800 (0%)	1
Presyncope	1/2791 (0%)	1	0/2800 (0%)	0
Subarachnoid haemorrhage	1/2791 (0%)	1	1/2800 (0%)	1
Syncope	4/2791 (0.1%)	4	2/2800 (0.1%)	2
Transient ischaemic attack	1/2791 (0%)	1	2/2800 (0.1%)	2
Trigeminal neuralgia	1/2791 (0%)	1	0/2800 (0%)	0
Product Issues
Device failure	0/2791 (0%)	0	1/2800 (0%)	1
Psychiatric disorders
Bipolar disorder	2/2791 (0.1%)	2	0/2800 (0%)	0
Confusional state	1/2791 (0%)	1	1/2800 (0%)	1
Delirium	1/2791 (0%)	1	1/2800 (0%)	1
Depression	1/2791 (0%)	1	2/2800 (0.1%)	2
Mania	0/2791 (0%)	0	1/2800 (0%)	1
Mental disorder	1/2791 (0%)	1	0/2800 (0%)	0
Psychotic disorder	0/2791 (0%)	0	1/2800 (0%)	1
Suicide attempt	1/2791 (0%)	1	2/2800 (0.1%)	2
Renal and urinary disorders
Acute kidney injury	4/2791 (0.1%)	4	0/2800 (0%)	0
Nephrolithiasis	3/2791 (0.1%)	3	1/2800 (0%)	1
Renal failure	2/2791 (0.1%)	2	0/2800 (0%)	0
Renal impairment	1/2791 (0%)	1	0/2800 (0%)	0
Tubulointerstitial nephritis	0/2791 (0%)	0	1/2800 (0%)	1
Reproductive system and breast disorders
Adenomyosis	1/2770 (0%)	1	0/2785 (0%)	0
Breast atrophy	0/2791 (0%)	0	1/2800 (0%)	2
Breast calcifications	0/2791 (0%)	0	1/2800 (0%)	1
Breast discharge	0/2791 (0%)	0	1/2800 (0%)	1
Breast disorder	1/2791 (0%)	1	0/2800 (0%)	0
Breast fibrosis	0/2791 (0%)	0	1/2800 (0%)	1
Breast inflammation	0/2791 (0%)	0	1/2800 (0%)	1
Breast mass	1/2791 (0%)	1	0/2800 (0%)	0
Breast necrosis	1/2791 (0%)	1	0/2800 (0%)	0
Breast pain	0/2791 (0%)	0	1/2800 (0%)	1
Breast swelling	0/2791 (0%)	0	1/2800 (0%)	1
Cervical dysplasia	2/2770 (0.1%)	2	0/2785 (0%)	0
Endometrial disorder	0/2770 (0%)	0	1/2785 (0%)	1
Endometrial hypertrophy	0/2770 (0%)	0	2/2785 (0.1%)	2
Endometrial thickening	1/2770 (0%)	1	1/2785 (0%)	1
Endometriosis	0/2770 (0%)	0	1/2785 (0%)	1
Fibrocystic breast disease	0/2791 (0%)	0	2/2800 (0.1%)	2
Metrorrhagia	0/2770 (0%)	0	1/2785 (0%)	1
Ovarian cyst	0/2770 (0%)	0	3/2785 (0.1%)	3
Pelvic haematoma	1/2791 (0%)	1	0/2800 (0%)	0
Uterine polyp	2/2770 (0.1%)	2	3/2785 (0.1%)	3
Respiratory, thoracic and mediastinal disorders
Asthma	0/2791 (0%)	0	1/2800 (0%)	1
Chronic obstructive pulmonary disease	1/2791 (0%)	3	0/2800 (0%)	0
Dyspnoea	2/2791 (0.1%)	2	1/2800 (0%)	1
Hypoxia	2/2791 (0.1%)	2	0/2800 (0%)	0
Interstitial lung disease	2/2791 (0.1%)	2	0/2800 (0%)	0
Organising pneumonia	1/2791 (0%)	1	0/2800 (0%)	0
Pleural effusion	2/2791 (0.1%)	3	2/2800 (0.1%)	2
Pneumonia aspiration	0/2791 (0%)	0	1/2800 (0%)	1
Pneumonitis	7/2791 (0.3%)	7	0/2800 (0%)	0
Pulmonary embolism	16/2791 (0.6%)	16	3/2800 (0.1%)	4
Respiratory failure	2/2791 (0.1%)	2	1/2800 (0%)	1
Skin and subcutaneous tissue disorders
Erythema	0/2791 (0%)	0	1/2800 (0%)	1
Vascular disorders
Deep vein thrombosis	16/2791 (0.6%)	17	3/2800 (0.1%)	4
Embolism	1/2791 (0%)	1	0/2800 (0%)	0
Haematoma	0/2791 (0%)	0	1/2800 (0%)	1
Haemorrhage	1/2791 (0%)	1	1/2800 (0%)	1
Hypertension	1/2791 (0%)	1	0/2800 (0%)	0
Jugular vein thrombosis	0/2791 (0%)	0	1/2800 (0%)	1
Lymphoedema	5/2791 (0.2%)	5	3/2800 (0.1%)	3
Peripheral artery thrombosis	1/2791 (0%)	1	1/2800 (0%)	2
Thrombophlebitis	2/2791 (0.1%)	2	0/2800 (0%)	0
Thrombophlebitis superficial	1/2791 (0%)	1	0/2800 (0%)	0
Other (Not Including Serious) Adverse Events
	150 mg Abemaciclib + Endocrine Therapy		Endocrine Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2723/2791 (97.6%)		2318/2800 (82.8%)
Blood and lymphatic system disorders
Anaemia	634/2791 (22.7%)	862	88/2800 (3.1%)	113
Leukopenia	1026/2791 (36.8%)	1706	171/2800 (6.1%)	244
Lymphopenia	372/2791 (13.3%)	527	94/2800 (3.4%)	118
Neutropenia	1246/2791 (44.6%)	2316	140/2800 (5%)	214
Thrombocytopenia	341/2791 (12.2%)	528	39/2800 (1.4%)	48
Cardiac disorders
Palpitations	54/2791 (1.9%)	62	20/2800 (0.7%)	22
Ear and labyrinth disorders
Vertigo	70/2791 (2.5%)	93	47/2800 (1.7%)	55
Endocrine disorders
Hypothyroidism	28/2791 (1%)	29	34/2800 (1.2%)	34
Eye disorders
Dry eye	71/2791 (2.5%)	76	28/2800 (1%)	31
Lacrimation increased	137/2791 (4.9%)	158	10/2800 (0.4%)	10
Vision blurred	46/2791 (1.6%)	52	24/2800 (0.9%)	25
Gastrointestinal disorders
Abdominal distension	75/2791 (2.7%)	90	27/2800 (1%)	28
Abdominal pain	945/2791 (33.9%)	1974	226/2800 (8.1%)	275
Constipation	288/2791 (10.3%)	377	142/2800 (5.1%)	161
Diarrhoea	2294/2791 (82.2%)	11663	199/2800 (7.1%)	288
Dry mouth	94/2791 (3.4%)	103	25/2800 (0.9%)	27
Dyspepsia	205/2791 (7.3%)	264	61/2800 (2.2%)	66
Flatulence	84/2791 (3%)	95	11/2800 (0.4%)	12
Gastritis	58/2791 (2.1%)	65	31/2800 (1.1%)	34
Gastrooesophageal reflux disease	74/2791 (2.7%)	76	45/2800 (1.6%)	47
Haemorrhoids	68/2791 (2.4%)	82	28/2800 (1%)	28
Mouth ulceration	39/2791 (1.4%)	48	3/2800 (0.1%)	3
Nausea	779/2791 (27.9%)	1203	222/2800 (7.9%)	274
Stomatitis	154/2791 (5.5%)	212	30/2800 (1.1%)	39
Toothache	49/2791 (1.8%)	55	42/2800 (1.5%)	50
Vomiting	454/2791 (16.3%)	744	117/2800 (4.2%)	144
General disorders
Axillary pain	28/2791 (1%)	28	39/2800 (1.4%)	41
Chest pain	35/2791 (1.3%)	40	35/2800 (1.3%)	36
Chills	49/2791 (1.8%)	55	18/2800 (0.6%)	18
Fatigue	1073/2791 (38.4%)	1434	433/2800 (15.5%)	522
Influenza like illness	141/2791 (5.1%)	180	112/2800 (4%)	152
Malaise	88/2791 (3.2%)	109	29/2800 (1%)	29
Mucosal inflammation	72/2791 (2.6%)	90	21/2800 (0.8%)	32
Oedema peripheral	169/2791 (6.1%)	200	103/2800 (3.7%)	119
Pain	60/2791 (2.1%)	64	53/2800 (1.9%)	58
Peripheral swelling	51/2791 (1.8%)	58	53/2800 (1.9%)	61
Pyrexia	227/2791 (8.1%)	299	114/2800 (4.1%)	130
Hepatobiliary disorders
Hepatic steatosis	41/2791 (1.5%)	42	35/2800 (1.3%)	35
Infections and infestations
Bronchitis	42/2791 (1.5%)	50	40/2800 (1.4%)	44
Cellulitis	37/2791 (1.3%)	43	28/2800 (1%)	31
Conjunctivitis	55/2791 (2%)	63	30/2800 (1.1%)	34
Gastroenteritis	73/2791 (2.6%)	84	32/2800 (1.1%)	36
Herpes zoster	34/2791 (1.2%)	34	39/2800 (1.4%)	39
Influenza	110/2791 (3.9%)	139	102/2800 (3.6%)	135
Nasopharyngitis	231/2791 (8.3%)	324	186/2800 (6.6%)	285
Oral herpes	29/2791 (1%)	34	8/2800 (0.3%)	9
Pharyngitis	26/2791 (0.9%)	29	29/2800 (1%)	33
Pneumonia	45/2791 (1.6%)	46	19/2800 (0.7%)	19
Sinusitis	69/2791 (2.5%)	76	51/2800 (1.8%)	67
Skin infection	33/2791 (1.2%)	36	23/2800 (0.8%)	26
Upper respiratory tract infection	280/2791 (10%)	393	214/2800 (7.6%)	323
Urinary tract infection	278/2791 (10%)	368	167/2800 (6%)	235
Vaginal infection	30/2770 (1.1%)	37	18/2785 (0.6%)	21
Viral infection	28/2791 (1%)	32	14/2800 (0.5%)	15
Vulvovaginal candidiasis	29/2770 (1%)	33	20/2785 (0.7%)	31
Injury, poisoning and procedural complications
Contusion	42/2791 (1.5%)	51	37/2800 (1.3%)	38
Fall	52/2791 (1.9%)	61	36/2800 (1.3%)	43
Procedural pain	73/2791 (2.6%)	78	53/2800 (1.9%)	64
Investigations
Alanine aminotransferase increased	265/2791 (9.5%)	345	119/2800 (4.3%)	149
Aspartate aminotransferase increased	257/2791 (9.2%)	323	106/2800 (3.8%)	122
Blood alkaline phosphatase increased	83/2791 (3%)	98	47/2800 (1.7%)	56
Blood creatinine increased	277/2791 (9.9%)	396	17/2800 (0.6%)	22
Gamma-glutamyltransferase increased	70/2791 (2.5%)	80	24/2800 (0.9%)	28
Weight decreased	79/2791 (2.8%)	88	19/2800 (0.7%)	20
Weight increased	29/2791 (1%)	32	46/2800 (1.6%)	47
Metabolism and nutrition disorders
Decreased appetite	312/2791 (11.2%)	352	54/2800 (1.9%)	57
Dehydration	33/2791 (1.2%)	39	7/2800 (0.3%)	7
Hypercalcaemia	49/2791 (1.8%)	58	32/2800 (1.1%)	42
Hypercholesterolaemia	48/2791 (1.7%)	53	61/2800 (2.2%)	67
Hyperglycaemia	37/2791 (1.3%)	51	43/2800 (1.5%)	53
Hypertriglyceridaemia	67/2791 (2.4%)	82	45/2800 (1.6%)	63
Hyperuricaemia	33/2791 (1.2%)	44	13/2800 (0.5%)	14
Hypoalbuminaemia	30/2791 (1.1%)	39	12/2800 (0.4%)	17
Hypokalaemia	105/2791 (3.8%)	126	22/2800 (0.8%)	31
Vitamin d deficiency	29/2791 (1%)	33	33/2800 (1.2%)	37
Musculoskeletal and connective tissue disorders
Arthralgia	571/2791 (20.5%)	705	876/2800 (31.3%)	1117
Arthritis	9/2791 (0.3%)	10	29/2800 (1%)	33
Back pain	223/2791 (8%)	277	271/2800 (9.7%)	317
Bone pain	62/2791 (2.2%)	75	93/2800 (3.3%)	102
Joint range of motion decreased	24/2791 (0.9%)	35	29/2800 (1%)	40
Joint stiffness	22/2791 (0.8%)	25	56/2800 (2%)	59
Muscle spasms	134/2791 (4.8%)	180	100/2800 (3.6%)	121
Muscular weakness	29/2791 (1%)	31	16/2800 (0.6%)	16
Musculoskeletal chest pain	70/2791 (2.5%)	77	72/2800 (2.6%)	76
Musculoskeletal pain	111/2791 (4%)	120	154/2800 (5.5%)	170
Musculoskeletal stiffness	32/2791 (1.1%)	34	33/2800 (1.2%)	37
Myalgia	167/2791 (6%)	193	163/2800 (5.8%)	185
Neck pain	48/2791 (1.7%)	49	59/2800 (2.1%)	64
Osteopenia	30/2791 (1.1%)	30	32/2800 (1.1%)	32
Osteoporosis	45/2791 (1.6%)	45	71/2800 (2.5%)	75
Pain in extremity	245/2791 (8.8%)	292	274/2800 (9.8%)	354
Nervous system disorders
Dizziness	274/2791 (9.8%)	333	158/2800 (5.6%)	188
Dysgeusia	103/2791 (3.7%)	121	8/2800 (0.3%)	8
Headache	482/2791 (17.3%)	809	359/2800 (12.8%)	553
Memory impairment	29/2791 (1%)	32	22/2800 (0.8%)	22
Neuropathy	193/2791 (6.9%)	221	203/2800 (7.3%)	234
Taste disorder	36/2791 (1.3%)	36	4/2800 (0.1%)	4
Psychiatric disorders
Anxiety	81/2791 (2.9%)	84	113/2800 (4%)	116
Depression	134/2791 (4.8%)	142	116/2800 (4.1%)	120
Insomnia	208/2791 (7.5%)	251	218/2800 (7.8%)	246
Renal and urinary disorders
Dysuria	46/2791 (1.6%)	53	25/2800 (0.9%)	29
Reproductive system and breast disorders
Breast pain	95/2791 (3.4%)	104	120/2800 (4.3%)	133
Erectile dysfunction	1/21 (4.8%)	1	0/15 (0%)	0
Vaginal discharge	26/2770 (0.9%)	27	39/2785 (1.4%)	42
Vulvovaginal dryness	78/2770 (2.8%)	80	117/2785 (4.2%)	127
Respiratory, thoracic and mediastinal disorders
Cough	337/2791 (12.1%)	407	193/2800 (6.9%)	228
Dyspnoea	139/2791 (5%)	154	77/2800 (2.8%)	86
Epistaxis	49/2791 (1.8%)	52	8/2800 (0.3%)	10
Nasal congestion	34/2791 (1.2%)	37	29/2800 (1%)	33
Oropharyngeal pain	115/2791 (4.1%)	142	76/2800 (2.7%)	91
Pneumonitis	36/2791 (1.3%)	36	10/2800 (0.4%)	10
Productive cough	45/2791 (1.6%)	53	25/2800 (0.9%)	28
Rhinitis allergic	40/2791 (1.4%)	41	40/2800 (1.4%)	42
Rhinorrhoea	29/2791 (1%)	31	15/2800 (0.5%)	16
Skin and subcutaneous tissue disorders
Alopecia	254/2791 (9.1%)	266	53/2800 (1.9%)	53
Dermatitis	28/2791 (1%)	31	11/2800 (0.4%)	13
Dry skin	102/2791 (3.7%)	108	48/2800 (1.7%)	51
Eczema	29/2791 (1%)	32	28/2800 (1%)	31
Erythema	38/2791 (1.4%)	43	26/2800 (0.9%)	28
Hyperhidrosis	29/2791 (1%)	33	32/2800 (1.1%)	34
Nail disorder	43/2791 (1.5%)	45	4/2800 (0.1%)	4
Night sweats	40/2791 (1.4%)	43	28/2800 (1%)	31
Onychoclasis	46/2791 (1.6%)	54	7/2800 (0.3%)	7
Pruritus	219/2791 (7.8%)	298	110/2800 (3.9%)	121
Rash	272/2791 (9.7%)	332	106/2800 (3.8%)	132
Surgical and medical procedures
Breast reconstruction	28/2791 (1%)	28	22/2800 (0.8%)	25
Vascular disorders
Hot flush	393/2791 (14.1%)	432	587/2800 (21%)	678
Hypertension	101/2791 (3.6%)	120	130/2800 (4.6%)	158
Hypotension	33/2791 (1.2%)	33	14/2800 (0.5%)	15
Lymphoedema	282/2791 (10.1%)	295	207/2800 (7.4%)	225

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.