Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)

Metastatic Breast Cancer Clinical Trial

Official title:

MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01942135
• Other study ID #: A5481023
• Secondary ID: 2013-002580-26
• Status: Completed
• Phase: Phase 3
• Start date: September 26, 2013
• Est. completion date: September 28, 2022

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 521
• Est. completion date: September 28, 2022
• Est. primary completion date: December 5, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women 18 years or older with metastatic or locally advanced disease, not amenable to curative therapy

• Confirmed diagnosis of HR+/HER2- breast cancer

• Any menopausal status

• Progressed within 12 months from prior adjuvant or progressed within 1 month from prior advanced/metastatic endocrine breast cancer therapy

• On an LHRH agonist for at least 28 days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ®) at time of randomization.

• Measurable disease defined by RECIST version 1.1, or bone-only disease

• Eastern Cooperative Oncology Group (ECOG) PS 0-1

• Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures

• Patient must agree to provide tumor tissue from metastatic tissue at baseline

Exclusion Criteria:

• Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway

• Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases

• Major surgery or any anti-cancer therapy within 2 weeks of randomization

• Prior stem cell or bone marrow transplantation

• Use of potent CYP3A4 inhibitors or inducers

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Palbociclib
Palbociclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
• Fulvestrant
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.
• Placebo
Placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
• Fulvestrant
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.

Locations

Country	Name	City	State
Australia	River City Pharmacy	Auchenflower	Queensland
Australia	Bankstown - Lidcombe Hospital	Bankstown	New South Wales
Australia	Cabrini Brighton	Brighton	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Peninsula and Southeast Oncology	Frankston	Victoria
Australia	Barwon Health, University Hospital Geelong	Geelong	Victoria
Australia	Cabrini Hospital	Malvern	Victoria
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Peter MacCallum Cancer Centre Pharmacy	Melbourne	Victoria
Australia	Fiona Stanley Hospital - Cancer Centre	Murdoch	Western Australia
Australia	Sunshine Coast Hospital and Health Service	Nambour	Queensland
Australia	Icon Cancer Care Southport	Southport	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Sunshine Hospital Clinical Trials Pharmacy	St Albans	Victoria
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Belgium	Imelda Ziekenhuis	Bonheiden
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Hopital Erasme	Bruxelles	Region DE Bruxelles-capital
Belgium	Institut Jules Bordet	Bruxelles	Bruxelles Capitale
Belgium	Grand Hôpital de Charleroi - Site Notre Dame	Charleroi	Hainaut
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	INDC Entité Jolimontoise - CH de Jolimont-Lobbes	Haine St. Paul	Hainaut
Belgium	UZ Leuven - Campus Gasthuisberg	Leuven
Belgium	C.H. de l'Ardenne - site Libramont	Libramont-Chevigny	Luxembourg
Belgium	CHU UCL Namur - Site Sainte-Elisabeth	Namur
Belgium	Clinique Saint-Pierre	Ottignies	Brabant Wallon
Belgium	CHWaPi - Site IMC	Tournai	Hainaut
Belgium	GZA Ziekenhuizen - Campus St Augustinus	Wilrijk
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	British Columbia Cancer Agency - Sindi Ahluwalia Hawkins Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario @ Kingston Health Sciences Centre	Kingston	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Lakeridge Health Oshawa, R.S. McLaughlin Durham Regional Cancer Centre	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre, General Campus	Ottawa	Ontario
Canada	Niagara Health System Walker Family Cancer Center	St. Catharines	Ontario
Canada	British Columbia Cancer Agency - Fraser Valley Centre	Surrey	British Columbia
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Germany	Universitaetsklinikum Leipzig AoeR	Leipzig
Germany	Zentrum fuer Radiologie und Nuklearmedizin am Johannisplatz	Leipzig
Germany	Klinikum der Universität München	München
Germany	Klinikum der Universität München	München
Ireland	Bon Secours Hospital	Cork
Italy	Azienda Sanitaria Firenze, c/o Ospedale S. M. Annunziata Farmacia Interna	Bagno A Ripoli (FI)
Italy	S.O.C. Oncologia Medica I, Azienda Sanitaria Firenze, c/o Ospedale S. M. Annunziata	Bagno A Ripoli (FI)
Italy	SSD Oncologia Medica Addarii-Zamagni A.O.U. di Bologna Policlinico S. Orsola Malpighi	Bologna
Italy	U.O. di Oncologia Medica P.O. Policlinico G. Rodolico"	Catania
Italy	Azienda U.L.S.S. n. 21 di Legnago, Presidio Ospedaliero Mater Salutis	Legnago (VR)
Italy	Farmacia Ospedaliera-Azienda U.L.S.S. n. 21 di Legnago	Legnago (VR)
Italy	IRST, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola (FC)
Italy	Farmacia IRCCS Ospedale San Raffaele	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IRCCS Ospedale S. Raffaele	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Servizio di Farmacia - Istituto Europeo di Oncologia	Milano
Italy	Policlinico di Modena Dipartimento ad attivita integrata di Oncologia,	Modena
Italy	IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori	Napoli
Italy	Farmacia - Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	S.C. Oncologia, A.O.S. Maria	Terni
Japan	Chiba Cancer Center	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Saitama Cancer Center	Kita-adachi-gun	Saitama,japan
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama-city	Ehime
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	National Hospital Organization	Osaka
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Haga Ziekenhuis	Den Haag	Zuid-holland
Netherlands	Leids Universitair Medisch Centrum	Leiden	Zuid-holland
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht	Limburg
Netherlands	Ikazia Ziekenhuis	Rotterdam	Zuid-holland
Netherlands	Orbis Medisch Centrum	Sittard-Geleen	Limburg
Netherlands	TweeSteden Ziekenhuis	Tilburg	Noord-brabant
Portugal	Champalimaud Cancer Center/ Breast Unit	Lisboa
Portugal	Instituto Português de Oncologia	Porto
Romania	Spitalul Clinic CF nr.2 Bucuresti	Bucharest
Romania	Spitalul Municipal Ploiesti	Ploiesti
Romania	Spitalul Judetean de Urgente "Sf. Ioan cel Nou"	Suceava
Romania	Spitalul Clinic Judetean Mures	Tg. Mures
Russian Federation	OGBUZ Belgorod Oncology Dispensary	Belgorod,	Belgorodskaya Oblast',
Russian Federation	GBUZ Chelyabinsk regional clinical center of oncology and nuclear medicine	Chelyabinsk
Russian Federation	FGBUZ Clinical Hospital 101 of the Federal Medical and Biological Agency"	Lermontov	Stavropol Territory
Russian Federation	FSBSI Russian Cancer Research Center n.a.NN Blokhin	Moscow
Russian Federation	GBUZ of Stavropol Territory "Pyatigorsk Oncology Dispensary"	Pyatigorsk,	Stavropol Territory
Russian Federation	Saint Petersburg GBUZ "City Clinical Oncology Dispensary"	Saint Petersburg
Russian Federation	Saint Petersburg GBUZ City Clinical Oncology Dispensary	Saint Petersburg
Russian Federation	OGBUZ Belgorod Oncology Dispensary	Stariy Oskol	Belgorodskaya Oblast'
Russian Federation	GBUZ of Stavropol Territory "Stavropol Regional Clinical Oncology Dispensary"	Stavropol
Russian Federation	GBUZ Republican Clinical Oncology Dispensary of Ministry of Health of the Republic of Bashkortostan	Ufa	Republic OF Bashkortostan
Russian Federation	GBUZ Leningrad regional oncological dispensary	Village Kuzmolovsky	Leningradskaya Oblast'
Russian Federation	FGBU Russian Research Center for Radiology and Surgical Technologies	Village Pesochny
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Ege University Medical Faculty	Izmir	Bornova
Ukraine	Oblasne komunalne nekomertsiine pidpryiemstvo "Bukovynskyi klinichnyi onkolohichnyi tsentr"	Chernivtsi
Ukraine	Komunalnyi zaklad 'Miska klinichna likarnia No.4' Dniprovskoi miskoi rady,	Dnipro
Ukraine	Komunalne nekomertsiyne pidpryiemstvo "Oblasnyi	Kharkiv
Ukraine	KNP Lvivskoi oblasnoi rady Lvivskyi onkolohichnyi	Lviv
Ukraine	Komunalna ustanova "Odeska oblasna klinichna likarnia"	Odesa
Ukraine	Podilskyi rehionalnyi tsentr onkolohii,	Vinnytsia
United Kingdom	Velindre Cancer Centre	Cardiff	South Glamorgan
United Kingdom	The Royal Marsden NHS Foundation Trust	London
United Kingdom	Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust Portsmouth Haematology and Oncology Centre	Portsmouth	Hampshire
United Kingdom	Royal Hallamshire Hospital	Sheffield	South Yorkshire
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust, Weston Park Hospital	Sheffield	South Yorkshire
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United States	University of Michigan Health System/Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Virginia Cancer Specialists, PC	Arlington	Virginia
United States	Hope Women's Cancer Centers	Asheville	North Carolina
United States	Mission Hospital, Inc.	Asheville	North Carolina
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	ATTN - Research Pharmacist	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)	Aurora	Colorado
United States	Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital	Austell	Georgia
United States	Mount Sinai Medical Center- Aventura	Aventura	Florida
United States	Arizona Center for Cancer Care	Avondale	Arizona
United States	CBCC Global Research Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Mercy Clinic St. Louis Cancer and Breast Institute	Ballwin	Missouri
United States	Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins	Baltimore	Maryland
United States	UAB Hospital-Investigational Drug Service	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham, The Kirklin Clinic	Birmingham	Alabama
United States	CareMount Medical	Brewster	New York
United States	Maine Center for Cancer Medicine, dba: New England Cancer Specialists	Brunswick	Maine
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Cartersville	Georgia
United States	Ironwood Physicians P.C dba Ironwood Cancer & Research Centers	Chandler	Arizona
United States	Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	Mercy Ministry Office	Chesterfield	Missouri
United States	Rush University Medical Center	Chicago	Illinois
United States	Administrative Management Only: Translational Research Management	Culver City	California
United States	Texas Oncology- Dallas Presbyterian Hospital	Dallas	Texas
United States	Southern Cancer Center, PC	Daphne	Alabama
United States	Sylvester Comprehensive Cancer Center Deerfield Beach	Deerfield Beach	Florida
United States	University of Miami Hospitals and Clinics (UHMC) Sylvester at Deerfield Beach	Deerfield Beach	Florida
United States	City of Hope	Duarte	California
United States	Fairview Southdale Oncology Clinic	Edina	Minnesota
United States	Inova Medical Group	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Piedmont Cancer Institute, PC	Fayetteville	Georgia
United States	Arizona Oncology Associates, PC- HAL	Flagstaff	Arizona
United States	Holy Cross Hospital/Michael and Dianne Bienes Comprehensive Cancer Center	Fort Lauderdale	Florida
United States	Investigational Products Center (IPC)	Fort Worth	Texas
United States	St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare	Fullerton	California
United States	The Jones Clinic, PC	Germantown	Tennessee
United States	Ironwood Physicians P.C dba Ironwood Cancer & Research Centers	Gilbert	Arizona
United States	Arizona Center for Cancer Care	Glendale	Arizona
United States	Global Research Management	Glendale	California
United States	Palo Verde Hematology Oncology	Glendale	Arizona
United States	Western Regional Medical Center, Inc.	Goodyear	Arizona
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Memorial Breast Cancer Center at Memorial Regional Hospital	Hollywood	Florida
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Memorial Regional Hospital	Hollywood	Florida
United States	US Oncology Investigational Products Center (IPC)	Irving	Texas
United States	US Oncology lnvestigational Products Center (IPC)	Irving	Texas
United States	Maine Center for Cancer Medicine, dba: New England Cancer Specialists	Kennebunk	Maine
United States	UC San Diego Medical Center-La Jolla	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	ProHEALTHCARE Associates, LLP	Lake Success	New York
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Virginia Cancer Specialists, PC	Leesburg	Virginia
United States	Texas Oncology- Longview Cancer Center	Longview	Texas
United States	Keck Hospital of USC	Los Angeles	California
United States	LAC & USC Medical Center	Los Angeles	California
United States	UCLA Hematology Oncology	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station	Lutherville	Maryland
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia
United States	Northwest Georgia Oncology Centers, PC	Marietta	Georgia
United States	Texas Oncology- McAllen South Second Street	McAllen	Texas
United States	Columbia St. Mary's	Mequon	Wisconsin
United States	Ironwood Physicians P.C dba Ironwood Cancer & Research Centers	Mesa	Arizona
United States	Ironwood Physicians P.C dba Ironwood Cancer & Research Centers	Mesa	Arizona
United States	University of Miami Hospitals & Clinics	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Columbia St. Mary's	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota
United States	University of Minnesota Physicians, Masonic Cancer Center	Minneapolis	Minnesota
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	Southern Cancer Center,PC	Mobile	Alabama
United States	UPMC Cancer Center, Monroeville	Monroeville	Pennsylvania
United States	CareMount Medical	Mount Kisco	New York
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Orlando Health	Ocoee	Florida
United States	Breastlink Medical Group, Inc.	Orange	California
United States	Hematology Oncology Medical Group of Orange County, Inc. (HOMG)	Orange	California
United States	The Center for Cancer Prevention and Treatment at St. Joseph Hospital of Orange	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	UCLA Hematology/Oncology - Pasadena	Pasadena	California
United States	Memorial Breast Cancer Center at Memorial Hospital West	Pembroke Pines	Florida
United States	Memorial Cancer Institute at Memorial Hospital West	Pembroke Pines	Florida
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Magee Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center, William M. Cooper Pavilion, Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Sylvester at Plantation	Plantation	Florida
United States	Arizona Oncology Associates, PC- HAL	Prescott Valley	Arizona
United States	Mercy Clinic St. Louis Cancer and Breast Institute	Saint Louis	Missouri
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	Mercy Hospital St.Louis- David C. Pratt Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Hospital	Salt Lake City	Utah
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	UC San Diego Medical Center-Hillcrest	San Diego	California
United States	University of California, San Francisco: Helen Diller Comprehensive Cancer Center	San Francisco	California
United States	San Luis Obispo Oncology and Hematology Health Center/Pacific Central Coast Health Centers	San Luis Obispo	California
United States	Breastlink Medical Group, Inc.	Santa Ana	California
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California
United States	Maine Center for Cancer Medicine, dba: New England Cancer Specialists	Scarborough	Maine
United States	Swedish Cancer Institute	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Swedish Medical Center First Hill IDS Pharmacy	Seattle	Washington
United States	Arizona Oncology Associates, PC- HAL	Sedona	Arizona
United States	City of Hope	South Pasadena	California
United States	Arizona Center for Cancer Care	Surprise	Arizona
United States	Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates	Torrance	California
United States	Torrance Memorial Physician Network-Cancer Care	Torrance	California
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	The University of Arizona Cancer Center- North Campus	Tucson	Arizona
United States	Texas Oncology- Tyler	Tyler	Texas
United States	Virginia Oncology Associates	Virginia Beach	Virginia
United States	Texas Oncology- Weslaco	Weslaco	Texas
United States	Wellness Oncology & Hematology	West Hills	California
United States	UCLA Hematology - Oncology Clinic - Westlake Village	Westlake Village	California
United States	Shenandoah Oncology, P.C.	Winchester	Virginia
United States	Cancer Treatment Centers of America at Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Romania,  Russian Federation,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) as Assessed by the Investigator	PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =[progression/death date(censor date) - randomization date + 1]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.	From randomization date to date of first documentation of progression or death (assessed up to 12 months)
Secondary	Overall Survival (OS)-Number of Participants Who Died	OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = [death date (censor date) - randomization date + 1]/30.4.	From randomization until death (up to 4.5 years)
Secondary	Overall Survival (OS)	OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = [death date (censor date) - randomization date + 1]/30.4.	From randomization until death (up to 4.5 years)
Secondary	Survival Probabilities at Year 1, Year 2, and Year 3	One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive.	From randomization until death (assessed up to 36 months)
Secondary	Objective Response (OR)	OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR.	From randomization until end of treatment (assessed up to 2 years)
Secondary	Duration of Response (DR)	DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1)]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR.	From randomization until end of treatment (assessed up to 2 years)
Secondary	Clinical Benefit Response (CBR)	CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) =24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD =24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD =24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD =24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, =30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.	From randomization until end of treatment (assessed up to 2 years)
Secondary	Observed Plasma Trough Concentration (Ctrough) for Palbociclib	Ctrough was defined as steady-state predose concentration. Observed directly from data. For palbociclib, a steady-state trough was to be defined as a predose plasma concentration following at least 8 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 22 and 26 hours after the dose (the day prior to PK collection) and no more than 1 hour post-dose on the day of PK collection.	Cycle 1/Day 15 and Cycle 2/Day 15
Secondary	Ctrough for Fulvestrant	Ctrough was defined as steady-state predose concentration. Observed directly from data. For fulvestrant, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.	Cycles 2/Day 1 and Cycle 3/Day 1
Secondary	Ctrough for Goserelin	Ctrough was defined as steady-state predose concentration. Observed directly from data. For goserelin, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.	Cycles 2/ Day 1 and Cycle 3/ Day 1
Secondary	Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores	The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores	The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores	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 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores	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 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms.	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores	The EuroQol-5D (version 3L) 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 three level scale (1=no problem, 2=some problem, and 3=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, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. 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).	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale	The EuroQol-5D (version 3L) 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).	From Cycle 1 to 14, as of 05 December 2014.
Secondary	Time to Deterioration (TTD)	A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of =10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below.	Baseline, Day 1 of Cycles 2 to 4, Day 1 of every alternate cycle after that until the end of treatment, as of 05 December 2014
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)	An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.	From the date of randomization up to 28 calendar days (±7 days) after last dose of study intervention (up to 8.4 years).
Secondary	Participants With Shifts From CTCAE Grade =2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Hematology Results	Number of participants with shifts from Grade =2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade =2 at baseline to Grade 3 or 4 postbaseline (for parameters Anemia, Hemoglobin increased, Neutrophil count decreased, Platelet count decreased, and White blood cell count decreased) were reported.	From baseline to end of treatment/withdrawal (up to 4.5 years)
Secondary	Participants With Shifts From CTCAE Grade =2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Chemistry Results	Number of participants with shifts from Grade =2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade =2 at baseline to Grade 3 or 4 postbaseline (for parameters ALT increased, ALP increased, AST increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypokalemia, Hypomagnesemia, and Hyponatremia) were reported.	From baseline to end of treatment/withdrawal (up to 4.5 years)

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