A Study of Neoadjuvant Letrozole + Taselisib Versus Letrozole + Placebo in Post-Menopausal Women With Breast Cancer (LORELEI)

A Phase II Randomized, Double-Blind Study of Neoadjuvant Letrozole Plus GDC-0032 Versus Letrozole Plus Placebo in Postmenopausal Women With ER-positive/HER2-negative, Early Stage Breast Cancer

This is a two-arm, randomized, double-blind, multicenter, pre-operative study to evaluate the effect of combining letrozole and GDC-0032 (also known as taselisib) versus letrozole and placebo in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2) untreated, Stage I-III operable breast cancer. Participants will be randomized into one of the two treatment arms with a 1:1 randomization ratio. Letrozole at 2.5 milligrams (mg) will be dosed once daily plus either Taselisib at 4 mg (two 2-mg tablets) or placebo on a 5 days-on/ 2 days-off schedule for a total of 16 weeks.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Letrozole; Other: Placebo; Drug: Taselisib

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre; St Vincents Hospital
    • Waratah, New South Wales, Australia, 2298
      • Newcastle Mater Misericordiae Hospital; Oncology
  • Victoria
    • East Melbourne, Victoria, Australia
      • Victorian Breast and Oncology Care
    • Malvern, Victoria, Australia, 3144
      • Cabrini Medical Centre; Oncology
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Graz, Austria, 8036
    • Lkh-Univ. Klinikum Graz; Klinik Für Gynäkologie
  • Graz, Austria, 8036
    • LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
  • Innsbruck, Austria, 6020
    • Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie
  • Linz, Austria, 4010
    • Ordensklinikum Linz Barmherzige Schwestern ; Abt. f. Allgemein- und Viszeralchirurgie
  • Salzburg, Austria, 5020
    • Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
  • St. Veit/Glan, Austria, 9300
    • Brustzentrum - Ordination Dr. Wette
  • Wels, Austria, 4600
    • Klinikum Kreuzschwestern Wels; Iii. Interne Abt.
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie
  • Wien, Austria, 1130
    • Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Chirurgie - Abt. für Allgemeinchirurgie
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Bruxelles, Belgium, 1020
    • CHU Brugmann (Victor Horta)
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Namur, Belgium, 5000
    • Clinique Ste-Elisabeth
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • SC
    • Itajai, SC, Brazil, 88301-220
      • Clinica de Neoplasias Litoral
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • São Paulo, SP, Brazil, 03102-002
      • Instituto Brasileiro De Controle Do Câncer - IBCC; Laboratório De Patologia
• Chile
  • Viña del Mar, Chile, 2520612
    • Hospital Clinico Vina del Mar
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
  • Pardubice, Czechia, 532 03
    • MULTISCAN, s.r.o., Radiologicke centrum Pardubice
  • Pribram, Czechia, 261 01
    • Oblastni nemocnice Pribram
• El Salvador
  • Salvador, El Salvador, 01101
    • Hospital Oncologia; Oncology
• France
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin; Division De Recherche Clinique
  • Le Mans, France, 72015
    • Centre Jean Bernard
  • Paris, France, 75231
    • Institut Curie; Oncologie Medicale
  • Paris, France, 75475
    • Hopital Saint Louis; Service Onco Thoracique
  • Saint Cloud, France, 92210
    • Centre Rene Huguenin; ONCOLOGIE GENETIQUE
  • Toulon, France, 83056
    • CHI de Toulon - Hôpital Sainte Musse
  • Vandoeuvre-Les-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine
• Germany
  • Berlin, Germany, 14169
    • Studienzentrum Berlin City
  • Berlin, Germany, 10367
    • Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)
  • Bielefeld, Germany, 33604
    • Onkologische Schwerpunktpraxis Bielefeld
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
  • Essen, Germany, 45136
    • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
  • Gelsenkirchen, Germany, 45879
    • Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe
  • Muenchen, Germany, 80637
    • Rotkreuzklinikum München; Frauenklinik
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe
  • Ulm, Germany, 89075
    • Universitätsklinikum Ulm Am Michelsberg; Frauenklinik
  • Witten, Germany, 58452
    • Marien-Hospital Witten; Frauenklinik Brustzentrum
• Guatemala
  • Guatemala, Guatemala, 01010
    • Centro Oncológico Sixtino / Centro Oncológico SA
  • Guatemala City, Guatemala, 01015
    • Grupo Angeles
• Hungary
  • Budapest, Hungary, 1032
    • Szent Margit Hospital; Dept. of Oncology
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika
  • Kecskemet, Hungary, 6000
    • Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont
  • Miskolc, Hungary, 3526
    • B-A-Z County Hospital
  • Szeged, Hungary, 6720
    • Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
    • Rimini, Emilia-Romagna, Italy, 47923
      • Ospedale Degli Infermi
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Uni Degli Studi Di Genova ; Clinica Di Medicina Interna Ad Indirizzo Oncologico
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
      • ASST DI CREMONA; Dip. Medicina - S.C. Oncologia
    • Legnago, Lombardia, Italy, 37045
      • Ospedale Per Acuti Mater Salutis Di Legnago
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 410-769
    • National Cancer Center; Medical Oncology
  • Seoul, Korea, Republic of, 03080
    • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Severance Hospital; Medical Oncology
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Centre; Division of Hematology/Oncology
• Mexico
  • Chihuahua, Mexico, 31000
    • Centro Estatal de Cancerología
  • Distrito Federal, Mexico, 14000
    • Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios
  • Mexico City, Mexico, 03100
    • Consultorio de Medicina Especializada; Dentro de Condominio San Francisco
• Panama
  • Panama, Panama, 0834-02723
    • Centro Oncologico America
• Peru
  • Lima, Peru, Lima 41
    • Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional
  • Lima, Peru, 41
    • Oncosalud Sac; Oncología
  • Lima, Peru, 31
    • Hospital Nacional Cayetano Heredia; Hematology - Oncology
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
  • Gdańsk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
  • Lodz, Poland, 93-513
    • Wojewódzki Szpital Specjalistyczny im. M. Kopernika; Oddział Chemioterapii
  • Otwock, Poland, 05-400
    • Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii; im. Marii Skłodowskiej-Curie
  • Warszawa, Poland, 02-781
    • Cent.Onkologii-Instytut im. M. S-Curie, Klinika Now. Piersi i Chirurgii Rekon
• Portugal
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa; Servico de Oncologia Medica
  • Lisboa, Portugal, 1400-038
    • Centro Clinico Champalimaud; Oncologia Medica
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Barcelona, Spain, 08028
    • Instituto Universitario Dexeus; Servicio de Oncología
  • Caceres, Spain, 10003
    • Hospital San Pedro De Alcantara; Servicio de Oncologia
  • Castellon, Spain, 12002
    • Hospital Provincial de Castellon; Servicio de Oncologia
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
  • Jaen, Spain, 23007
    • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
  • Lerida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
  • Madrid, Spain, 28943
    • Hospital Universitario de Fuenlabrada; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario; Oncologia
  • Valencia, Spain, 46980
    • Fundación IVO
  • Cordoba
    • Córdoba, Cordoba, Spain, 14004
      • Hospital Universitario Reina Sofia; Servicio de Oncologia
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
• Switzerland
  • Baden, Switzerland, 5405
    • Kantonsspital Baden; Frauenklinik
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden;Onkologie und Hämatologie
  • Locarno, Switzerland, 6600
    • Fondazione Oncologia Lago Maggiore
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth General Hospital; Oncology
  • Camberley, United Kingdom, GU16 7UJ
    • Frimley Park Hospital; Breast Resaerch Team
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Manchester, United Kingdom, M20 3BG
    • Christie Hospital
• United States
  • California
    • Santa Ana, California, United States, 92705
      • Breastlink Med Group Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • MGH Cancer Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSKCC at Basking Ridge
  • New York
    • Commack, New York, United States, 11725
      • MSKCC @ Commack
    • Harrison, New York, United States, 10604
      • MSKCC @ West Harrison
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
    • Rockville Centre, New York, United States, 11570
      • MSKC @ Rockville
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female participants
• Postmenopausal status
• Histologically confirmed invasive breast carcinoma, with all of the following characteristics: (i) Primary tumor greater than or equal to (>/=) 2 centimeters (cm) in largest diameter (cT1-3) by MRI; (ii) Stage I to operable Stage III breast cancer; (iii) Documented absence of distant metastases (M0)
• Estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer
• Breast cancer eligible for primary surgery
• Tumor tissue from formalin-fixed paraffin-embedded cores (FFPE) core biopsy of breast primary tumor that is confirmed as evaluable for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation status by central histopathology laboratory
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Fasting glucose less than or equal to (</=) 125 milligrams per deciliter (mg/dL)
• Adequate hematological, renal, and hepatic function
• Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol, in the investigator's judgment

Exclusion Criteria:

• Any prior treatment for primary invasive breast cancer
• Participants with cT4 or cN3 stage breast tumors
• Bilateral invasive, multicentric, or metastatic breast cancer
• Participants who have undergone excisional biopsy of primary tumor and/or axillary lymph nodes or sentinel lymph node biopsy
• Type 1 or 2 diabetes requiring antihyperglycemic medication
• Inability or unwillingness to swallow pills
• Malabsorption syndrome or other condition that would interfere with enteric absorption
• History of prior or currently active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis). Any predisposition for gastrointestinal (GI) toxicity requires prior approval from the Medical Monitor.
• Congenital long QT syndrome or QT interval corrected using Fridericia's formula (QTcF) >470 milliseconds (msec)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) <60% of the predicted values
• Clinically significant (i.e., active) cardiovascular disease, uncontrolled hypertension, unstable angina, history of myocardial infarction, cardiac failure class II-IV
• Any contraindication to MRI examination
• Active infection requiring intravenous antibiotics
• Participants requiring any daily supplemental oxygen
• Clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis
• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the participants at high risk from treatment complications
• Significant traumatic injury within 3 weeks prior to initiation of study treatment
• Major surgical procedure within 4 weeks prior to initiation of study treatment
• Inability to comply with study and follow-up procedures
• History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Letrozole + Placebo; Participants will receive 2.5 mg letrozole tablets orally QD along with placebo on a 5-days-on/2-days-off schedule for a total of 16 weeks.	Drug: Letrozole; Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.; Other: Placebo; Placebo tablets matched to taselisib formulation will be administered orally daily on 5 days-on/2 days-off schedule for up to 16 weeks.
EXPERIMENTAL: Letrozole + Taselisib; Participants will receive 2.5 milligrams (mg) letrozole tablets orally once daily (QD) along with taselisib tablets at 4 mg (two 2 mg tablets) orally on a 5 days-on/2 days-off schedule for a total of 16 weeks.	Drug: Letrozole; Letrozole tablets will be administered orally at 2.5 mg QD for 16 weeks.; Drug: Taselisib; Taselisib will be administered orally at 4 mg (two 2 mg tablets) daily.; Other Names: GDC-0032

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR) by Centrally Assessed Breast Magnetic Resonance Imaging (MRI) Via Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Version 1.1	Objective response rate (ORR) was defined as proportion of participants achieving complete response (CR) or partial response (PR). As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With Total Pathologic Complete Response (Total pCR), Defined as Having pCR in Both Breast and Axilla, Using American Joint Committee on Cancer (AJCC) Staging System	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks
Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) Mutant (MT) Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With Total pCR , Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA MT Participants	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With OR by Centrally Assessed Breast MRI Via mRECIST Version 1.1 in PIK3CA Wildtype (WT) Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With Total pCR Defined as Having pCR in Both Breast and Axilla, Using AJCC Staging System in PIK3CA WT Participants	Total pCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes (i.e., ypT0/Tis, ypN0 in the AJCC staging system, 7th edition).	From Baseline to 16 weeks
Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With OR by Breast Ultrasound Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With OR by Mammography Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA MT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Percentage of Participants With OR by Clinical Breast Exam (Palpation) Via mRECIST Version 1.1 in PIK3CA WT Participants	ORR was defined as proportion of participants achieving CR or PR. As per modified RECIST v1.1, CR: disappearance of all target lesions, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	From Baseline to 16 weeks
Central Assessments of Changes in Ki67 Levels	Ki67 is a prognostic marker and is used to evaluate the proliferative activity of breast cancer.	From Baseline to Week 3 and Surgery (Weeks 17-18); and Week 3 to Surgery (Weeks 17-18)
Preoperative Endocrine Prognostic Index (PEPI ) Score	To obtain the PEPI score, risk points for relapse-free survival (RFS) and breast cancer-specific survival (BCSS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each participant is the sum of the risk points derived from the primary tumor (pT) stage, regional lymph nodes (pN) stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each participant is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).	Week 16
Percent Change From Baseline to Surgery in Enhancing Tumor Volume as Measured by Breast MRI		From Baseline to Surgery (Weeks 17-18)
Mean Score for Health-Related Quality of Life Measured by the European Organization for Research C30 (EORTC QLQ-C30)	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). The last 2 questions represented the participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. Here, Post surgery= PS.	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Mean Score for Treatment of Cancer Quality of Life Questionnaire BR23 (QLQ-BR23)	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 enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. Here, Post surgery= PS.	Weeks 1, 5, 9, 13, 16, 4-week Post-Surgery
Percentage of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to 22 weeks

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Breast International Group; SOLTI Breast Cancer Research Group; Austrian Breast and Colorectal Cancer Group

Publications and helpful links

General Publications

• Eiger D, Brandao M, de Azambuja E. Lessons learned at SABCS 2019 and to-dos from immunotherapy in breast cancer. ESMO Open. 2020 Mar;5(2):e000688. doi: 10.1136/esmoopen-2020-000688. No abstract available.
• Eiger D, Franzoi MA, Ponde N, Brandao M, de Angelis C, Schmitt Nogueira M, de Hemptinne Q, de Azambuja E. Cardiotoxicity of trastuzumab given for 12 months compared to shorter treatment periods: a systematic review and meta-analysis of six clinical trials. ESMO Open. 2020 Feb;5(1):e000659. doi: 10.1136/esmoopen-2019-000659.
• Saura C, Hlauschek D, Oliveira M, Zardavas D, Jallitsch-Halper A, de la Pena L, Nuciforo P, Ballestrero A, Dubsky P, Lombard JM, Vuylsteke P, Castaneda CA, Colleoni M, Santos Borges G, Ciruelos E, Fornier M, Boer K, Bardia A, Wilson TR, Stout TJ, Hsu JY, Shi Y, Piccart M, Gnant M, Baselga J, de Azambuja E. Neoadjuvant letrozole plus taselisib versus letrozole plus placebo in postmenopausal women with oestrogen receptor-positive, HER2-negative, early-stage breast cancer (LORELEI): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2019 Sep;20(9):1226-1238. doi: 10.1016/S1470-2045(19)30334-1. Epub 2019 Aug 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 12, 2014
• Primary Completion (ACTUAL): March 13, 2017
• Study Completion (ACTUAL): March 13, 2017

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (ESTIMATE): October 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: GO28888; 2013-000568-28 (EUDRACT_NUMBER)