Phase 2 Study of Amcenestrant (SAR439859) Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer

Breast Cancer Metastatic Clinical Trial

— AMEERA-3  

Official title:

An Open Label Randomized Phase 2 Trial of Amcenestrant (SAR439859), Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04059484
• Other study ID #: ACT16105
• Secondary ID: U1111-1217-27742
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 22, 2019
• Est. completion date: September 30, 2024

Study information

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

Clinical Trial Summary

Primary Objective:

To determine whether amcenestrant per overall survival (os) improves progression free survival (PFS) when compared with an endocrine monotherapy of the choice of the physician, in participants with metastatic or locally advanced breast cancer

Secondary Objectives:

• To compare the overall survival in the 2 treatment arms

• To assess the objective response rate in the 2 treatment arms

• To evaluate the disease control rate in the 2 treatment arms

• To evaluate the clinical benefit rate in the 2 treatment arms

• To evaluate the duration of response in the 2 treatment arms

• To evaluate the PFS according to the estrogen receptor 1 gene (ESR1) mutation status in the 2 treatment arms

• To evaluate the pharmacokinetics of amcenestrant as single agent

• To evaluate health-related quality of life in the 2 treatment arms

• To compare the overall safety profile in the 2 treatment arms

Description:

The duration of the study for an individual participant will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (28 days of study treatment), and an end of treatment (EOT) visit at least 30 days (or until the participant receive another anticancer therapy, whichever is earlier) following the last administration of study treatment. Study treatment may continue until precluded by unacceptable toxicity, disease progression, death or upon participant's request to stop treatment, or Investigator decision, whichever occurs first.

An extension of recruitment for Chinese participants is planned in this study: After completion of randomization in the global part of the study, randomization will continue in China until approximately 90 Chinese participants are randomized.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 367
• Est. completion date: September 30, 2024
• Est. primary completion date: February 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• 18 years or older.

• Histological or cytological diagnosis of adenocarcinoma of the breast.

• Locally advanced not amenable to radiation therapy or surgery in a curative intent, and/or metastatic disease.

• Estrogen receptor(ER) positive status.

• Human epidermal growth factor receptor 2 negative status.

• Participants must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease.

• In the main study, a prior treatment with a Cyclin-dependent kinase 4 and 6(CDK 4/6) inhibitor is mandatory if this treatment is approved and can be reimbursed for this participant. The percentage of participants without previous CDK 4/6 inhibitor will be capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6 inhibitor will not be mandatory, and there will be no limitation to the number of participants naïve to CDK4/6 inhibitor.

• Participants must present a secondary endocrine resistance to endocrine therapy defined as: progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy.

• Male or Female.

Exclusion criteria:

• Eastern Cooperative Oncology Group performance status =>2.

• Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant. Participants unable to swallow normally and to take capsules.

• Participant with any other cancer. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant has been disease free for greater than 3 years are allowed.

• Severe uncontrolled systemic disease at screening .

• Participants with known brain metastases that are untreated, symptomatic or require therapy to control symptoms.

• Prior treatment with mammalian target of rapamycin inhibitors or any other selective estrogen receptor degrader(SERD) compound, except fulvestrant if stopped for at least 3 months before randomization.

• Treatment with drugs that have the potential to inhibit Uridine'5 Diphospho-Glucuronosyl Transferase(UGT) less than 2 weeks before randomization.

• Treatment with strong Cytochrome P450 (CYP)3A inducers within 2 weeks before randomization.

• Ongoing treatment with drugs that are sensitive substrate of organic anion transporting polypeptide 1B1/B3(OATP1B1/B3) (asunaprevir, atorvastatin, bosentan, danoprevir, fexofenadine, glyburide, nateglinide, pitavastatin, pravastatin, replaglinide, rosuvastatin, and simvastatin acid).

• Treatment with anticancer agents (including investigational drugs) less than 3 weeks before randomization.

• Inadequate hematological, coagulation, renal and liver functions.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms

Intervention

Drug:
• Amcenestrant
Pharmaceutical form: Capsule Route of administration: Oral
• Fulvestrant
Pharmaceutical form: Solution for injection Route of administration: Intramuscular
• Anastrozole
Pharmaceutical form:Tablets or capsules Route of administration: Oral
• Letrozole
Pharmaceutical form: Tablets or capsules Route of administration: Oral
• Exemestane
Pharmaceutical form: Tablets or capsules Route of administration: Oral
• Tamoxifen
Pharmaceutical form: Tablets or capsules Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Buenos Aires
Argentina	Investigational Site Number : 0320006	Buenos Aires
Argentina	Investigational Site Number : 0320008	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320007	Capital Federal	Buenos Aires
Argentina	Investigational Site Number : 0320004	La Rioja
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320002	Salta
Australia	Investigational Site Number : 0360001	Nedlands	Western Australia
Australia	Investigational Site Number : 0360003	South Brisbane	Queensland
Australia	Investigational Site Number : 0360002	Woolloongabba	Queensland
Belgium	Investigational Site Number : 0560002	Charleroi
Belgium	Investigational Site Number : 0560001	Leuven
Belgium	Investigational Site Number : 0560003	Namur
Brazil	Hospital Araujo Jorge Site Number : 0760005	Goiania	Goiás
Brazil	Hospital de Clinicas de Porto Alegre - HCPA Site Number : 0760001	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Mae de Deus Site Number : 0760002	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Base Sao Jose do Rio Preto Site Number : 0760003	Sao Jose do Rio Preto	São Paulo
Brazil	Nucleo de Pesquisa Clinica e Ensino da Rede Sao Camilo Site Number : 0760006	Sao Paulo	São Paulo
Canada	Investigational Site Number : 1240004	Calgary	Alberta
Canada	Investigational Site Number : 1240003	London	Ontario
Canada	Investigational Site Number : 1240006	Montreal	Quebec
China	Investigational Site Number : 1560001	Beijing
China	Investigational Site Number : 1560015	Changchun
China	Investigational Site Number : 1560014	Changsha
China	Investigational Site Number : 1560025	Chengdu
China	Investigational Site Number : 1560024	Chongqing
China	Investigational Site Number : 1560002	Hangzhou
China	Investigational Site Number : 1560023	Hangzhou
China	Investigational Site Number : 1560005	Harbin
China	Investigational Site Number : 1560010	Hefei
China	Investigational Site Number : 1560018	Hefei
China	Investigational Site Number : 1560026	Jinan
China	Investigational Site Number : 1560003	Kunming
China	Investigational Site Number : 1560008	Linyi
China	Investigational Site Number : 1560011	Nanjing
China	Investigational Site Number : 1560013	Tianjin
China	Investigational Site Number : 1560021	Urumqi
China	Investigational Site Number : 1560016	Wuhan
China	Investigational Site Number : 1560031	Xuzhou
Czechia	Investigational Site Number : 2030002	Brno
Czechia	Investigational Site Number : 2030003	Novy Jicin
Czechia	Investigational Site Number : 2030004	Praha 4
France	Investigational Site Number : 2500008	ANGERS Cedex 02
France	Investigational Site Number : 2500006	Creteil
France	Investigational Site Number : 2500007	Marseille
France	Investigational Site Number : 2500005	Paris
France	Investigational Site Number : 2500001	Villejuif
Greece	Investigational Site Number : 3000001	Heraklion
Greece	Investigational Site Number : 3000002	Larisa
Greece	Investigational Site Number : 3000004	Thessaloniki
Israel	Investigational Site Number : 3760002	Jerusalem
Israel	Investigational Site Number : 3760001	Petah-Tikva
Israel	Investigational Site Number : 3760003	Tel Aviv
Israel	Investigational Site Number : 3760004	Tel HaShomer
Italy	Investigational Site Number : 3800001	Candiolo	Torino
Italy	Investigational Site Number : 3800002	Milano
Italy	Investigational Site Number : 3800003	Prato
Japan	Investigational Site Number : 3920004	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920001	Kashiwa-shi	Chiba
Japan	Investigational Site Number : 3920005	Kitaadachi-gun	Saitama
Japan	Investigational Site Number : 3920008	Koto-ku	Tokyo
Japan	Investigational Site Number : 3920002	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920003	Osaka-shi	Osaka
Japan	Investigational Site Number : 3920009	Ota-shi	Gunma
Japan	Investigational Site Number : 3920006	Yokohama-shi	Kanagawa
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
Latvia	Investigational Site Number : 4280001	Riga
Latvia	Investigational Site Number : 4280002	Riga
Mexico	Investigational Site Number : 4840005	Mexico
Mexico	Investigational Site Number : 4840002	Monterrey	Nuevo León
Mexico	Investigational Site Number : 4840006	Veracruz
Poland	Investigational Site Number : 6160003	Poznan	Wielkopolskie
Poland	Investigational Site Number : 6160001	Warszawa	Mazowieckie
Puerto Rico	Torre Hospital Auxilo Mutuo Site Number : 8400028	Ponce De Leon 735 Hato Rey
Russian Federation	Investigational Site Number : 6430003	Moscow
Russian Federation	Investigational Site Number : 6430005	Moscow
Russian Federation	Investigational Site Number : 6430002	Saint -Petersburg
Spain	Investigational Site Number : 7240003	Barcelona	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240006	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240008	Málaga
Taiwan	Investigational Site Number : 1580002	Taichung
Taiwan	Investigational Site Number : 1580003	Tainan
Taiwan	Investigational Site Number : 1580001	Taipei
Taiwan	Investigational Site Number : 1580004	Taipei
Taiwan	Investigational Site Number : 1580005	Taipei
Turkey	Investigational Site Number : 7920004	Ankara
Turkey	Investigational Site Number : 7920002	Edirne
Turkey	Investigational Site Number : 7920003	Istanbul
Ukraine	Investigational Site Number : 8040001	Kryvyi Rih
Ukraine	Investigational Site Number : 8040004	Odesa
Ukraine	Investigational Site Number : 8040005	Uzhgorod
United States	Comprehensive Blood and Cancer Center Site Number : 8400018	Bakersfield	California
United States	Hematology Oncology Clinic Site Number : 8400020	Baton Rouge	Louisiana
United States	Alabama Oncology Site Number : 8400008	Birmingham	Alabama
United States	Dana Farber Cancer Institute Site Number : 8400015	Boston	Massachusetts
United States	University Of Vermont Site Number : 8400026	Burlington	Vermont
United States	Gabrail Cancer Center Site Number : 8400006	Canton	Ohio
United States	The University of Kansas Clinical Research Center Site Number : 8400027	Fairway	Kansas
United States	The Center For Cancer And Blood Disorders Site Number : 8400022	Fort Worth	Texas
United States	Hackensack University Medical Center Site Number : 8400025	Hackensack	New Jersey
United States	Saint Luke's Hospital Site Number : 8400032	Kansas City	Missouri
United States	Dartmouth Hitchcock Med Center Site Number : 8400013	Lebanon	New Hampshire
United States	University of Wisconsin Site Number : 8400016	Madison	Wisconsin
United States	UCLA Hematology Oncology Parkside Site Number : 8400024	Santa Monica	California
United States	Northwest Medical Specialties Site Number : 8400038	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine, 

References & Publications (1)

Tolaney SM, Chan A, Petrakova K, Delaloge S, Campone M, Iwata H, Peddi PF, Kaufman PA, De Kermadec E, Liu Q, Cohen P, Paux G, Wang L, Ternes N, Boitier E, Im SA. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrade — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the time in months interval 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 independent central review (ICR) 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: 116 weeks)
Secondary	Overall Survival (OS)	OS is defined as the time interval 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 is 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: 116 weeks)
Secondary	Percentage of Participants With Objective Response	Objective response is defined as percentage of participants having a partial response (PR) or complete response (CR) according to the RECIST version 1.1 assessed by ICR. 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: 116 weeks)
Secondary	Percentage of Participants With Disease Control	Disease control is defined as percentage of participants having a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: 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 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 progressive disease (PD), taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.	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: 116 weeks)
Secondary	Percentage of Participants With Clinical Benefit	Clinical Benefit is defined as percentage of participants having a confirmed CR, PR, SD, or Non-CR/Non-PD for at least 24 weeks determined by ICR as per RECIST 1.1 from the date of randomization to the date of end of treatment. As per RECIST 1.1, CR: 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. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Non-CR/Non-PD: persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.	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: 116 weeks)
Secondary	Duration of Response (DOR)	DOR is defined as time (in months) from first documented evidence of CR or PR until progressive disease (PD) determined by ICR as per RECIST 1.1 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: 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.	From the date of first response to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (maximum duration: 116 weeks)
Secondary	Progression Free Survival (PFS) According to Estrogen Receptor 1 Gene (ESR1) Mutation Status	PFS defined as the time (in months) interval from the date of randomization to the date of first documented tumor progression as per RECIST 1.1 assessed by ICR or death (due to any cause), whichever comes first. Progression 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. The mutation status (wild type, mutant) of twelve specific mutations of the ESR1 gene was determined by multiplex droplet digital polymerase chain reaction (ddPCR), including their mutant frequency and concentration. Here, PFS is reported based on the ESR1 mutation status of participants: wild type and mutants. ESR1 was the gene encoding estrogen receptor alpha. ESR1 mutant type breast cancer was a disease where the ESR1 gene had a mutation (i.e., a type of error). ESR1 wild type breast cancer was a disease where the ESR1 gene was normal without a mutation. Analysis was performed by Kaplan-Meier method.	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: 116 weeks)
Secondary	Pharmacokinetics: Plasma Concentrations of Amcenestrant	Amcenestrant plasma concentrations at specified time points are reported.	Cycle 1 Day 1: 1.5 hours(h), 4h post-dose, Day 15: pre-dose, Cycle 2 Day 1: pre-dose, 1.5h, 4h, 8h post-dose, Cycle 3 Day 1: pre-dose, Cycle 4 Day 1: pre-dose, Cycle 6 Day 1: pre-dose
Secondary	Within-Participant Steady State Ctrough of Amcenestrant	Within-participant Steady state Ctrough was defined as the median value of the Ctrough across study using plasma concentration of predose samples at Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 for each individual participant. Average (mean) of all calculated Ctrough values for all participants across study (Cycle 1 Day 15 and Day 1 of Cycle 2, 3, 4 and 6 ) was derived and reported in this outcome measure.	Predose on Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 6 Day 1
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) and 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) 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 30]) was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 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 30]) was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 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	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 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 overall treatment (i.e., each cycle [Cycle 1 up to Cycle 30]) was reported in this outcome measure.	Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 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 impact of breast cancer & side effects of treatment. EORTC-QLQ-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 to 100. Higher score for functional scales = better outcome; higher score for symptoms scales = higher symptom burden. 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 30]) was reported.	Baseline, overall treatment duration (Cycle 1 up to Cycle 30 [i.e.,116 weeks])