Amcenestrant (SAR439859) Plus Palbociclib as First Line Therapy for Patients With ER (+) HER2(-) Advanced Breast Cancer

Breast Cancer Clinical Trial

— AMEERA-5  

Official title:

A Randomized, Multicenter, Double-blind Phase 3 Study of Amcenestrant (SAR439859) Plus Palbociclib Versus Letrozole Plus Palbociclib for the Treatment of Patients With ER (+), HER2 (-) Breast Cancer Who Have Not Received Prior Systemic Anti-cancer Treatment for Advanced Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04478266
• Other study ID #: EFC15935
• Secondary ID: 2020-001824-33U1
• Status: Terminated
• Phase: Phase 3
• Start date: October 14, 2020
• Est. completion date: May 26, 2023

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To determine whether Amcenestrant (SAR439859) in combination with palbociclib improves progression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received any prior systemic anticancer therapies for advanced disease. Secondary Objective: - To compare the overall survival in both treatment arms. - To evaluate the objective response rate in both treatment arms. - To evaluate the duration of response in both treatment arms. - To evaluate the clinical benefit rate in both treatment arms. - To evaluate progression-free survival on next line of therapy. - To evaluate the pharmacokinetics of amcenestrant, and palbociclib. - To evaluate health-related quality of life in both treatment arms. - To evaluate the time to first chemotherapy in both treatment arms. - To evaluate safety in both treatment arms.

Description:

Study duration per participant was approximately 59 months, which includes a 33- month treatment period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1068
• Est. completion date: May 26, 2023
• Est. primary completion date: June 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Adult participants with loco-regional recurrent or metastatic disease not amenable to curative treatment.
• Confirmed diagnosis of ER+/HER2- breast cancer.
• No prior systemic treatment for loco-regional recurrent or metastatic disease.
• Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Participants should be willing to provide tumor tissue.
• Capable of giving informed consent.

Exclusion criteria:

• Known active brain metastases.
• Prior neo (adjuvant) treatment with any selective estrogen receptor degrader (SERD).
• Inadequate organ and marrow function.
• Disease recurrence while on, or within 12 months of completion of (neo)adjuvant endocrine therapy.
• Pregnant, breastfeeding, or woman of childbearing potential unwilling to use recommended contraception methods.
• Male participants who disagree to follow contraception.
• Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term.
• Participants with significant concomitant illness. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Amcenestrant-matching placebo
Pharmaceutical form: Tablets Route of Administration: Oral
• SAR439859
Pharmaceutical form: Tablets Route of Administration: Oral
• Palbociclib
Pharmaceutical form: Capsules/Tablets Route of Administration: Oral
• Letrozole
Pharmaceutical form: Capsules Route of Administration: Orally
• Goserelin
Pharmaceutical form: Depot Injection Route of Administration: Subcutaneous
• Letrozole-matching placebo
Pharmaceutical form: Capsules Route of Administration: Orally

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320004	Buenos Aires
Argentina	Investigational Site Number :0320001	Caba	Buenos Aires
Argentina	Investigational Site Number :0320005	Caba	Buenos Aires
Argentina	Investigational Site Number :0320008	Capital Federal	Buenos Aires
Argentina	Investigational Site Number :0320010	Cordoba	Córdoba
Argentina	Investigational Site Number :0320003	La Rioja
Argentina	Investigational Site Number :0320009	Mar del Plata
Argentina	Investigational Site Number :0320006	Pergamino	Buenos Aires
Argentina	Investigational Site Number :0320002	Rosario	Santa Fe
Argentina	Investigational Site Number :0320007	Salta
Australia	Investigational Site Number :0360004	Macquarie Park	New South Wales
Australia	Investigational Site Number :0360001	Nedlands	Western Australia
Australia	Investigational Site Number :0360005	Randwick	New South Wales
Australia	Investigational Site Number :0360002	Richmond	Victoria
Australia	Investigational Site Number :0360003	Wahroonga	New South Wales
Austria	Investigational Site Number :0400001	Graz
Belgium	Investigational Site Number :0560003	Bruxelles
Belgium	Investigational Site Number :0560004	Charleroi
Belgium	Investigational Site Number :0560001	Leuven
Belgium	Investigational Site Number :0560002	Namur
Brazil	Investigational Site Number :0760005	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760006	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760004	Rio De Janeiro
Brazil	Investigational Site Number :0760003	Sao Paulo	São Paulo
Brazil	Investigational Site Number :0760007	Sao Paulo	São Paulo
Brazil	Investigational Site Number :0760008	São Paulo
Bulgaria	Investigational Site Number :1000004	Burgas
Bulgaria	Investigational Site Number :1000005	Dobrich
Bulgaria	Investigational Site Number :1000008	Russe
Bulgaria	Investigational Site Number :1000001	Sofia
Canada	Investigational Site Number :1240007	Greenfield Park	Quebec
Canada	Investigational Site Number :1240004	Kingston	Ontario
Canada	Investigational Site Number :1240005	Montreal	Quebec
Canada	Investigational Site Number :1240014	Montreal	Quebec
Canada	Investigational Site Number :1240002	Toronto	Ontario
Chile	Investigational Site Number :1520005	La Serena	Coquimbo
Chile	Investigational Site Number :1520011	Santaigo	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520006	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520007	Santiago
Chile	Investigational Site Number :1520003	Santiago de Chile
Chile	Investigational Site Number :1520009	Talca	Maule
Chile	Investigational Site Number :1520004	Temuco	La Araucanía
Chile	Investigational Site Number :1520001	Viña del Mar	Valparaíso
China	Investigational Site Number :1560038	Baoding
China	Investigational Site Number :1560008	Beijing
China	Investigational Site Number :1560035	Beijing
China	Investigational Site Number :1560003	Changchun
China	Investigational Site Number :1560036	Changchun
China	Investigational Site Number :1560013	Chengdu
China	Investigational Site Number :1560019	Chongqing
China	Investigational Site Number :1560021	Dalian
China	Investigational Site Number :1560031	Dalian
China	Investigational Site Number :1560054	Deyang
China	Investigational Site Number :1560043	Fuzhou
China	Investigational Site Number :1560025	Guangzhou
China	Investigational Site Number :1560002	Hangzhou
China	Investigational Site Number :1560005	Hangzhou
China	Investigational Site Number :1560006	Hangzhou
China	Investigational Site Number :1560007	Hangzhou
China	Investigational Site Number :1560011	Harbin
China	Investigational Site Number :1560041	Hefei
China	Investigational Site Number :1560018	Jinan
China	Investigational Site Number :1560046	Jinan
China	Investigational Site Number :1560051	Jining
China	Investigational Site Number :1560017	Linyi
China	Investigational Site Number :1560055	Luoyang
China	Investigational Site Number :1560048	Neijiang
China	Investigational Site Number :1560001	Shanghai
China	Investigational Site Number :1560037	Shaoguan
China	Investigational Site Number :1560028	Tianjin
China	Investigational Site Number :1560024	Wuhan
China	Investigational Site Number :1560033	Wuhan
China	Investigational Site Number :1560044	Xi'An
China	Investigational Site Number :1560045	Xi'an
China	Investigational Site Number :1560027	Xuzhou
China	Investigational Site Number :1560049	Yantai
China	Investigational Site Number :1560022	Zhengzhou
Czechia	Investigational Site Number :2030001	Brno
Czechia	Investigational Site Number :2030002	Praha 2
Finland	Investigational Site Number :2460001	Helsinki
Finland	Investigational Site Number :2460002	Tampere
Finland	Investigational Site Number :2460003	Turku
France	Investigational Site Number :2500009	Nice
France	Investigational Site Number :2500001	Paris
France	Investigational Site Number :2500003	Paris
France	Investigational Site Number :2500006	Poitiers
France	Investigational Site Number :2500007	Saint Cloud
France	Investigational Site Number :2500002	Saint-Herblain
France	Investigational Site Number :2500010	Strasbourg
France	Investigational Site Number :2500005	TOULOUSE Cedex 9
France	Investigational Site Number :2500004	Villejuif
Georgia	Investigational Site Number :2680005	Batumi
Georgia	Investigational Site Number :2680006	Kutaisi
Georgia	Investigational Site Number :2680001	Tbilisi
Georgia	Investigational Site Number :2680002	Tbilisi
Georgia	Investigational Site Number :2680003	Tbilisi
Georgia	Investigational Site Number :2680004	Tbilisi
Georgia	Investigational Site Number :2680007	Tbilisi
Germany	Investigational Site Number :2760006	Bottrop
Germany	Investigational Site Number :2760003	Münster
Germany	Investigational Site Number :2760007	Oldenburg in Holstein
Germany	Investigational Site Number :2760001	Ulm
Hungary	Investigational Site Number :3480008	Budapest
Hungary	Investigational Site Number :3480005	Gyor
Hungary	Investigational Site Number :3480011	Gyula
Hungary	Investigational Site Number :3480003	Kaposvár
Hungary	Investigational Site Number :3480009	Kecskemét
Hungary	Investigational Site Number :3480010	Miskolc
Hungary	Investigational Site Number :3480001	Nyíregyháza
Italy	Investigational Site Number :3800010	Bologna
Italy	Investigational Site Number :3800008	Meldola (FC)	Emilia-Romagna
Italy	Investigational Site Number :3800002	Milano
Italy	Investigational Site Number :3800004	Milano
Italy	Investigational Site Number :3800007	Monza	Monza E Brianza
Italy	Investigational Site Number :3800006	Napoli
Italy	Investigational Site Number :3800005	Prato
Italy	Investigational Site Number :3800003	Rozzano	Milano
Japan	Investigational Site Number :3920013	Hidaka-shi	Saitama
Japan	Investigational Site Number :3920010	Hiroshima-shi	Hiroshima
Japan	Investigational Site Number :3920012	Kagoshima-shi	Kagoshima
Japan	Investigational Site Number :3920002	Kashiwa-shi	Chiba
Japan	Investigational Site Number :3920003	Koto-ku	Tokyo
Japan	Investigational Site Number :3920019	Kurume-shi	Fukuoka
Japan	Investigational Site Number :3920009	Matsuyama-shi	Ehime
Japan	Investigational Site Number :3920015	Meguro-ku	Tokyo
Japan	Investigational Site Number :3920022	Miyazaki-shi	Miyazaki
Japan	Investigational Site Number :3920007	Nagoya-shi	Aichi
Japan	Investigational Site Number :3920016	Nagoya-shi	Aichi
Japan	Investigational Site Number :3920008	Osaka-shi	Osaka
Japan	Investigational Site Number :3920018	Osaka-shi	Osaka
Japan	Investigational Site Number :3920001	Sapporo-shi	Hokkaido
Japan	Investigational Site Number :3920020	Sendai-shi	Miyagi
Japan	Investigational Site Number :3920005	Shinagawa-ku	Tokyo
Japan	Investigational Site Number :3920021	Shizuoka-shi	Shizuoka
Japan	Investigational Site Number :3920017	Takasaki-shi	Gunma
Japan	Investigational Site Number :3920006	Yokohama-shi	Kanagawa
Japan	Investigational Site Number :3920014	Yokohama-shi	Kanagawa
Korea, Republic of	Investigational Site Number :4100006	Goyang-si	Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100009	Seochogu
Korea, Republic of	Investigational Site Number :4100005	Seongnam	Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100008	Seongnam-si, Gyeonggi-do
Korea, Republic of	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100004	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number :4100007	Seoul	Seoul-teukbyeolsi
Netherlands	Investigational Site Number :5280006	Arnhem
Netherlands	Investigational Site Number :5280005	Delft
Netherlands	Investigational Site Number :5280001	Maastricht
Poland	Investigational Site Number :6160007	Poznan	Wielkopolskie
Poland	Investigational Site Number :6160002	Tomaszow Mazowiecki	Lódzkie
Portugal	Investigational Site Number :6200005	Almada
Portugal	Investigational Site Number :6200001	Lisboa
Portugal	Investigational Site Number :6200002	Porto
Russian Federation	Investigational Site Number :6430007	Arkhangelsk
Russian Federation	Investigational Site Number :6430004	Krasnogorskiy District
Russian Federation	Investigational Site Number :6430003	Moscow
Russian Federation	Investigational Site Number :6430005	Moscow
Russian Federation	Investigational Site Number :6430006	Moscow
Russian Federation	Investigational Site Number :6430008	Moscow
Russian Federation	Investigational Site Number :6430009	Moscow Region
Russian Federation	Investigational Site Number :6430001	Saint -Petersburg
Russian Federation	Investigational Site Number :6430010	Saint Petersburg
Singapore	Investigational Site Number :7020001	Singapore
Singapore	Investigational Site Number :7020002	Singapore
Singapore	Investigational Site Number :7020004	Singapore
South Africa	Investigational Site Number :7100004	Cape Town
South Africa	Investigational Site Number :7100006	Johannesburg
Spain	Investigational Site Number :7240011	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240008	Barcelona / Sabadell	Castilla Y León
Spain	Investigational Site Number :7240001	Madrid
Spain	Investigational Site Number :7240004	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number :7240002	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number :7240006	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number :7240007	Málaga
Spain	Investigational Site Number :7240003	Santiago de Compostela	Galicia [Galicia]
Spain	Investigational Site Number :7240005	Valencia	Valenciana, Comunidad
Spain	Investigational Site Number :7240009	Valencia
Taiwan	Investigational Site Number :1580007	Kaohsiung
Taiwan	Investigational Site Number :1580002	Tainan
Taiwan	Investigational Site Number :1580001	Taipei
Taiwan	Investigational Site Number :1580003	Taipei
Turkey	Investigational Site Number :7920006	Adana
Turkey	Investigational Site Number :7920008	Ankara
Turkey	Investigational Site Number :7920009	Ankara
Turkey	Investigational Site Number :7920007	Antalya
Turkey	Investigational Site Number :7920005	Bornova
Turkey	Investigational Site Number :7920013	Diyarbakir
Turkey	Investigational Site Number :7920003	Edirne
Turkey	Investigational Site Number :7920001	Istanbul
Turkey	Investigational Site Number :7920004	Istanbul
Turkey	Investigational Site Number :7920011	Istanbul
Turkey	Investigational Site Number :7920012	Izmir
Turkey	Investigational Site Number :7920010	Kocaeli
Turkey	Investigational Site Number :7920002	Malatya
Ukraine	Investigational Site Number :8040004	Kharkiv
Ukraine	Investigational Site Number :8040010	Kharkiv
Ukraine	Investigational Site Number :8040001	Kryvyi Rih
Ukraine	Investigational Site Number :8040002	Odesa
Ukraine	Investigational Site Number :8040007	Vinnytsia
United Kingdom	Investigational Site Number :8260005	Blackburn	Lancashire
United Kingdom	Investigational Site Number :8260002	Edinburgh	Edinburgh, City Of
United Kingdom	Investigational Site Number :8260001	Glasgow	Central Bedfordshire
United States	Investigational Site Number :8400002	Ann Arbor	Michigan
United States	Investigational Site Number :8400055	Athens	Georgia
United States	Investigational Site Number :8400016	Atlanta	Georgia
United States	Investigational Site Number :8400073	Austin	Texas
United States	Investigational Site Number :8400085	Blacksburg	Virginia
United States	Investigational Site Number :8400017	Boston	Massachusetts
United States	Investigational Site Number :8400039	Chicago	Illinois
United States	Investigational Site Number :8400070	Dallas	Texas
United States	Investigational Site Number :8400072	Dallas	Texas
United States	Investigational Site Number :8400076	Danvers	Massachusetts
United States	Investigational Site Number :8400075	Daphne	Alabama
United States	Investigational Site Number :8400080	Denton	Texas
United States	Investigational Site Number :8400025	Denver	Colorado
United States	Investigational Site Number :8400008	Fort Wayne	Indiana
United States	Investigational Site Number :8400038	Fullerton	California
United States	Investigational Site Number :8400083	Glendale	Arizona
United States	Investigational Site Number :8400061	Houston	Texas
United States	Investigational Site Number :8400068	Houston	Texas
United States	Investigational Site Number :8400006	Iowa City	Iowa
United States	Investigational Site Number :8400005	Kansas City	Missouri
United States	Investigational Site Number :8400059	Lakeland	Florida
United States	Investigational Site Number :8400058	Las Vegas	Nevada
United States	Investigational Site Number :8400056	Los Alamitos	California
United States	Investigational Site Number :8400015	New Brunswick	New Jersey
United States	Investigational Site Number :8400010	New York	New York
United States	Investigational Site Number :8400077	Newton	Massachusetts
United States	Investigational Site Number :8400053	Orlando	Florida
United States	Investigational Site Number :8400081	Palm Bay	Florida
United States	Investigational Site Number :8400024	Paramus	New Jersey
United States	Investigational Site Number :8400001	Pittsburgh	Pennsylvania
United States	Investigational Site Number :8400084	Plano	Texas
United States	Investigational Site Number :8400004	Saint Louis	Missouri
United States	Investigational Site Number :8400029	Santa Monica	California
United States	Investigational Site Number :8400034	Savannah	Georgia
United States	Investigational Site Number :8400028	Scarborough	Maine
United States	Investigational Site Number :8400023	Stony Brook	New York
United States	Investigational Site Number :8400086	The Woodlands	Texas
United States	Investigational Site Number :8400035	Thomasville	Georgia
United States	Investigational Site Number :8400067	Tigard	Oregon
United States	Investigational Site Number :8400066	Tucson	Arizona
United States	Investigational Site Number :8400078	Waco	Texas
United States	Investigational Site Number :8400082	Webster	Texas
United States	Investigational Site Number :8400013	Westwood	Kansas
United States	Investigational Site Number :8400069	Winchester	Virginia
United States	Investigational Site Number :8400009	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Czechia,  Finland,  France,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.	From randomization to the date of first documented tumor progression or death due to any cause or data cut-off date whichever comes first (maximum duration: 81 weeks)
Secondary	Overall Survival (OS)	OS was defined as the interval (in months) from the date of randomization to the date of documented death (due to any cause). In the absence of observation of death, survival time was censored to last date the participant was known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.	From randomization to the death due to any cause or data cut-off date, whichever comes first (maximum duration: 81 weeks)
Secondary	12-month Progression-free Survival (PFS) Rate	Percentage of participants who were disease progression-free at Month 12 after randomization were reported in this outcome measure. PFS was defined as the time interval (in months) from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by local radiologist or investigator, or death (due to any cause), whichever comes first. PD as per RECIST 1.1: at least a 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. The PFS rate at Month 12 was estimated using the Kaplan-Meier method and provided an estimation of the percentage of participants who were disease progression-free at Month 12 after randomization.	Month 12
Secondary	Percentage of Participants With Objective Response	Objective response was defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by investigator. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30%decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.	From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 81 weeks)
Secondary	Duration of Response (DOR)	DOR was defined as time (in months) from first documented evidence of CR or PR until disease progression determined by investigator as per RECIST 1.1, or start of any anti-cancer therapy, or death from any cause, whichever occurs first. For participants with ongoing response at the time of the analysis, DOR was censored at the date of the last valid disease assessment not showing documented progression performed before the initiation of a new anticancer treatment (if any). As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.	From the date of first response of CR or PR until disease progression or death, or start of any anti-cancer therapy or data cut-off date, whichever comes first (maximum duration: 81 weeks)
Secondary	Percentage of Participants With Clinical Benefit	Clinical Benefit was defined as the percentage of participants having a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by investigator as per RECIST 1.1, from date of randomization until disease progression, or death, or data cut-off date, or initiation of post treatment anti-cancer therapy, whichever occurs first. As per RECIST 1.1; CR was defined as disappearance of all target, non-target lesions & normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.	From randomization until disease progression, or death, or data cut-off date, whichever comes first (maximum duration: 81 weeks)
Secondary	Progression-free Survival on Next Line of Therapy (PFS2)	PFS2 was defined as the time interval (in months) from the date of randomization to the date of first documentation of PD on the next systemic anti-cancer therapy according to investigator, or death due to any cause in the absence of documented PD on the next systemic anti-cancer therapy, whichever occurs first. PD was defined as at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.	From randomization to date first documented disease progression on the next systemic anti-cancer therapy, or death due to any cause, or data cut-off date, whichever comes first (maximum duration: 81 weeks)
Secondary	Pharmacokinetics: Plasma Concentrations of Amcenestrant	Amcenestrant plasma concentrations at specified time points were reported. Data for this outcome measure was not planned to be collected and analyzed for Letrozole+Palbociclib arm as pre-specified in protocol.	Cycle 1 Day 1: 3 hours (hr) post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose
Secondary	Pharmacokinetics: Plasma Concentrations of Palbociclib	Palbociclib plasma concentrations at specified time points were reported.	Cycle 1 Day 1: 3 hr post-dose, Cycle 1 Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 3 hr post-dose, Cycle 2 Day 15: pre-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 7 Day 1: pre-dose, Cycle 10 Day 1: pre-dose
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30) Domain Scores	EORTC-QLQ-C30: cancer-specific instrument with 30 questions for evaluation of new chemotherapy & assessment of participant reported outcome. These include 5 functional scales, 9 symptom scales, & Global Health Status/quality of life scale (GHS/QoL). All 14 items/domains were scored on scale of 1 (not at all) to 4 (very much) & GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional & GHS/QoL=higher level of functioning, & higher score for symptoms scales=higher symptom burden. Least Square (LS) mean and Standard Error (SE) were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23) Domain Scores	QLQ-BR23: disease-specific Health-related QOL assesses breast cancer impact & side effects of treatment. EORTCQLQ- BR23 contains 23 items: multi-item scales & single-item measures. 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) & 4 scales related to symptoms of disease or treatment (arm symptoms, breast symptoms, systemic therapy side effects, & upset by hair loss). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0-100. Higher score for functional scales=better outcome; higher score for symptoms scales=higher symptom burden. LS mean & SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value & stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain was reported.	Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC QLQ-BR45) Domain Scores	EORTC QLQ-BR45: comprised of all 23 items from the QLQ-BR23 plus an additional 22 items assessing endocrine therapy symptoms (10 items), endocrine sexual symptoms (4 items), breast satisfaction (2 items), and skin mucosis symptoms (6 items). All items scored 1 (not at all) to 4 (very much). Scores of all scales transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. LS mean and SE are derived from Mixed Model Repeated Measures (MMRM) model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for each domain (endocrine therapy symptoms, endocrine sexual symptoms, breast satisfaction and skin mucosis symptoms) was reported.	Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
Secondary	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Visual Analog Scale (VAS) Score	EQ-5D-5L is a standardized measure of health status, provides a simple, generic measure of health for clinical and economic appraisal, and consists of 2 sections: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L VAS. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. LS mean and SE are derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values of overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for VAS was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
Secondary	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health Utility Index Value Score	EQ-5D-5L: consists of 2 sections: EQ-5D-5L health state utility index (descriptive system) & VAS. The EQ-5D descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, & extreme problems. Response options are measured with 5-point Likert scale (for 5L version). The EQ-5D-5L responses are converted into single index utility score between 0 to 1, where higher score indicates better health state & lower score indicate worse health state. LS mean and SE were derived from MMRM model with change from Baseline values as response variable, treatment, time, treatment-by-time interaction, Baseline value and stratifications factors as fixed effect. Average of LS mean change from Baseline values overall treatment (i.e., each cycle [Cycle 1 up to Cycle 21]) for health utility index value score was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 21 [i.e., 81 weeks])
Secondary	Time to First Chemotherapy	Time to chemotherapy was defined as the time interval (in months) from the date of randomization to the start date of the first chemotherapy after disease progression.	From randomization to the start date of the first chemotherapy (maximum duration: 81 weeks)
Secondary	Number of Participants With Hematological Abnormalities During the Treatment Period	Hematological parameters assessed were anemia, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, platelet count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 5.0 (NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment.	From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: 112 weeks)
Secondary	Number of Participants With Liver Function Abnormalities of Grade 3 and 4 During the Treatment Period	Liver Function parameters assessed were aspartate aminotransferase increased, alanine aminotransferase increased, alkaline phosphatase increased, total bilirubin increased, gamma-glutamyl transferase increased. Parameters were assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs. Treatment period was defined as the time from the first dose of study treatments up to 30 days after last dose of study treatment. Participants with Grade 3 and 4 liver function abnormalities were reported in this outcome measure.	From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: 112 weeks)