Trastuzumab in Treating Women With Primary Breast Cancer

Breast Cancer Clinical Trial

Official title:

HERA: A Randomised Three-Arm Multi-Centre Comparison Of 1 Year And 2 Years Of Herceptin Versus No Herceptin In Women With HER2-Positive Primary Breast Cancer Who Have Completed Adjuvant Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00045032
• Other study ID #: BO16348
• Secondary ID: BIG-01-01EU-2021
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 6, 2002
• Last updated: June 4, 2012
• Start date: December 2001
• Est. completion date: September 2015

Study information

• Verified date: March 2012
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Swedish Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether trastuzumab is effective in treating primary breast cancer in women who have completed adjuvant chemotherapy.

PURPOSE: This randomized phase III trial is studying two different regimens of trastuzumab and observation only to compare how well they work in treating women with breast cancer.

Description:

OBJECTIVES:

Primary

• Compare the disease-free survival of women with HER2-positive primary breast cancer treated with trastuzumab (Herceptin®) for 1 year vs trastuzumab for 2 years vs standard supportive care.

• Compare the overall survival of patients treated with these regimens.

• Compare the relapse-free survival of patients treated with these regimens.

• Compare the distant disease-free survival of patients treated with these regimens.

• Compare the incidence of cardiac dysfunction in patients treated with these regimens.

• Evaluate the safety and tolerability of these regimens in these patients.

Secondary

• Compare time to recurrence in patients treated with these regimens.

• Compare time to distant recurrence in patients treated with these regimens.

• Compare outcomes, in terms of disease-free survival, overall survival, recurrence-free survival, distant disease-free survival, time to recurrence, time to distant recurrence, cardiac safety, and overall safety, in patients treated with trastuzumab for 1 year vs 2 years.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to nodal status (any nodal status and prior neoadjuvant chemotherapy vs no positive nodes and no prior neoadjuvant chemotherapy vs 1-3 positive nodes and no prior neoadjuvant chemotherapy vs 4 or more positive nodes and no prior neoadjuvant chemotherapy), prior adjuvant chemotherapy regimen (no anthracyclines or taxanes vs anthracyclines only vs anthracyclines and taxanes), receptor status and endocrine therapy (negative vs positive and no prior endocrine therapy vs positive and prior endocrine therapy), age (18 to 34 vs 35 to 49 vs 50 to 59 vs 60 and over), and participating center. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive trastuzumab (Herceptin®) IV over 1.5 hours on day 1. Courses repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive trastuzumab as in arm I. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

• Arm III: Patients receive no trastuzumab. Patients may later receive trastuzumab as in arm I or arm II.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 4,482 patients (1,494 per treatment arm) will be accrued for this study within 4 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5043
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed nonmetastatic primary invasive adenocarcinoma of the breast

• Adequately excised

• Axillary nodes positive or negative

• No positive or suspicious internal mammary nodes identified by sentinel node technique that have not been irradiated

• No supraclavicular lymph node involvement

• HER2-positive disease with one of the following:

• 3+ overexpression by immunohistochemistry (IHC)

• 2+ overexpression by IHC and fluorescence in situ hybridization (FISH) with c-erbB2 gene amplification

• c-erbB2 gene amplification by FISH

• Previously treated with at least 3 months or 4 courses of approved neoadjuvant or adjuvant chemotherapy with or without radiotherapy

• No synchronous bilateral or multifocal breast cancer that is not HER2-positive

• No locally advanced or inflammatory breast cancer

• No clinical T4 primary breast tumor

• Prior curatively treated ipsilateral ductal carcinoma in situ of the breast is allowed

• Hormone receptor status:

• Estrogen receptor and progesterone receptor status known OR

• Estrogen receptor status known

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)

• AST and ALT no greater than 2.5 times ULN

• Alkaline phosphatase no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• LVEF at least 55% by echocardiography or MUGA

• No serious cardiac illness

• No documented congestive heart failure

• No high-risk uncontrolled arrhythmias

• No angina pectoris requiring antianginal medication

• No clinically significant valvular heart disease

• No evidence of transmural infarction on EKG

• No poorly controlled hypertension (i.e., systolic greater than 180 mm Hg or diastolic greater than 100 mm Hg)

Pulmonary

• No severe pulmonary disease/illness

Other

• No other malignancy except for curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other cancer that has been curatively treated, with no evidence of disease, and has less than 15% risk of recurrence over the next 10 years

• No other concurrent serious disease that would preclude study participation

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior peripheral stem cell or bone marrow stem cell transplantation as part of prior neoadjuvant or adjuvant chemotherapy regimen

• No prior biologic therapy or immunotherapy for breast cancer

• No prior anti-HER2 therapy for any reason

• No concurrent immunotherapy for breast cancer

Chemotherapy

• See Disease Characteristics

• See Biologic therapy

• No prior cumulative dose of doxorubicin more than 360 mg/m^2 or epirubicin more than 720 mg/m^2

• No prior anthracyclines for another malignancy

• No more than 7 weeks since day 1 of last chemotherapy course

• No concurrent adjuvant chemotherapy

Endocrine therapy

• No concurrent hormonal therapy, including aromatase inhibitors, pure antiestrogens, or progestational agents, for breast cancer

• Concurrent systemic adjuvant hormonal therapy for estrogen receptor-positive patients allowed

• Concurrent tamoxifen allowed

Radiotherapy

• See Disease Characteristics

• No more than 6 weeks since completion of prior radiotherapy

• No prior mediastinal irradiation except for internal mammary node irradiation for the present breast cancer

Surgery

• See Disease Characteristics

• No more than 6 weeks since prior definitive surgery

• Concurrent ovarian ablation allowed

Other

• No other concurrent investigational therapy for breast cancer

• Concurrent bisphosphonate therapy allowed if started prior to study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
Argentina	Hospital Aleman de Buenos Aires	Buenos Aires
Australia	Andrew Love Cancer Centre	Geelong	Victoria
Australia	Saint John of God Hospital	Geelong	Australian Capital Territory
Australia	Mount Hospital	Perth	Western Australia
Australia	Toowoomba Hospital	Toowoomba	Queensland
Austria	Landeskrankenhaus Feldkirch	Feldkirch-Tisis
Austria	Innsbruck Universitaetsklinik	Innsbruck
Austria	Landeskrankenhaus Klagenfurt	Klagenfurt
Austria	St. Vincent's Hospital	Linz Donau
Austria	Landeskrankenanstalten - Salzburg	Salzburg
Austria	Landeskrankenhaus St. Poelten	St. Poelten
Austria	Universitaetsklinik fuer Innere Medizin I	Vienna
Austria	Wilhelminenspital der Stadt Wien	Vienna
Austria	LKH Villach	Villach
Austria	LKH Voecklabruck	Voecklabruck
Austria	A. oe. Krankenhaus Wiener Neustadt	Wiener Neustadt
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp
Belgium	Reseau Hospitalier De Medecine Sociale	Baudour
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi
Belgium	Cazk Groeninghe - Campus St-Niklaas	Kortrijk
Belgium	Centre Hospitalier Universitaire de Tivoli	La Louviere
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Clinique Saint-Joseph	Liege
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	Hospital Serruys Ziekenhuis	Oostende
Belgium	Centre Hospitalier Peltzer-La Tourelle	Verviers
Brazil	Hospital Santa Rita	Porto Alegre
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre
Brazil	Porto Alegre Hospital	Porto Alegre	Rio Grande do Sul
Brazil	Instituto Nacional de Cancer	Rio de Janeiro
Brazil	Faculdade De Medicina Do ABC	Santo Andre
Canada	Royal Victoria Hospital of Barrie	Barrie	Ontario
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Prince Edward Island Cancer Centre at Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Trillium Health Centre - Mississauga Site	Mississauga	Ontario
Canada	Hopital du Saint-Sacrement, Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Algoma Regional Cancer Program at Sault Area Hospital	Sault Sainte Marie	Ontario
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Fraser Valley Cancer Centre at British Columbia Cancer Agency	Surrey	British Columbia
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	Hospital Clinico San Borja Arriaran	Santiago
Chile	Hospital Dr. Sotero Del Rio	Santiago
Chile	Hospital Militar	Santiago
Chile	Instituto Nacional Del Cancer	Santiago
China	Queen Mary Hospital	Hong Kong
China	Tuen Mun Hospital	Hong Kong
China	Tongji Medical University	Wuhan
Colombia	Instituto Nacional De Cancerologia	Bogota
Croatia	Clinical Hospital Center Split	Split
Denmark	Centralsygehus I Esbjerg	Esbjerg
Denmark	Herning Central Hospital	Herning
Denmark	Hillerod Hospital	Hillerod
Denmark	Centralsygehuset I Naestved	Naestved
Denmark	Sonderborg Sygehus	Sonderborg
France	Centre Regional Francois Baclesse	Caen
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Hopital Clinique Claude Bernard	Metz
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Evangelisches Bethesda Krankenhaus GmbH	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Martin Luther Universitaet	Halle
Germany	Henriettenstiftung Krankenhaus	Hanover
Germany	Universitaets-Hautklinik Heidelberg	Heidelberg
Germany	St. Vincentius-Kliniken	Karlsruhe
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Kreiskrankenhaus Leonberg - Frauenklinik	Leonberg
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	Frauenklinik Vom Roten Kreuz	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Frauenklinik - Universitaetsklinikum Rostock am Klinikum Sudstadt	Rostock
Germany	Universitaet Ulm	Ulm
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Greece	Evaggelismos Hospital	Athens
Greece	University of Crete School of Medicine	Heraklion	Crete
Guatemala	Centro Medico	Guatemala City
Guatemala	Hospital Roosevelt	Guatemala City
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
Hungary	Fovarosi Onkormanyzat Szent Margit Korhaz, Okologia	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	Semmelweis University	Budapest
Ireland	Cork University Hospital	Cork
Israel	Sieff Hospital	Safed
Italy	Ospedale San Lazzaro	Alba
Italy	Ospedale Presenti Fenaroli	Alzano-Lombardo
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Ospedale degli Infermi - ASL 12	Biella
Italy	Ospedale Bellaria	Bologna
Italy	Spedali Civili di Brescia	Brescia
Italy	Ospedale Oncologico A. Businco	Cagliari
Italy	Ospedale B. Ramazzini	Carpi
Italy	Ospedale Valduce	Como
Italy	Ospedale Santa Croce	Cuneo
Italy	Universita Degli Studi Di Florence	Firenze (Florence)
Italy	Azienda Ospedaliero Careggi	Florence
Italy	Morgagni-Pierantoni Ospedale	Forli
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa
Italy	Ospedale A. Manzoni	Lecco
Italy	Presidio Ospedaliero	Livorno
Italy	Carlo Poma Hospital	Mantova
Italy	European Institute of Oncology	Milan
Italy	Ospedale Niguarda Ca'Granda	Milan
Italy	University of Modena Hospital and Reggio Emilia School of Medicine	Modena
Italy	Azienda Ospedaliera Di Parma	Parma
Italy	I.R.C.C.S. Policlinico San Matteo	Pavia
Italy	Policlinico Monteluce	Perugia
Italy	Azienda Ospedaliera	Reggio Emilia
Italy	Ospedale San Filippo Neri	Rome
Italy	Ospedale Sant' Eugenio	Rome
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Ospedale Civile ASL 1	Sassari
Italy	Primario U.O. di Oncologia Medica	Trento
Italy	Ospedale Ostetrico Ginecologica Sant Anna	Turin
Italy	Universita di Torino	Turin
Japan	Tokai University School Of Medicine	Kanagawa
Japan	Tokyo Metropolitan - Komagome Hospital	Tokyo
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei Cancer Center at Yonsei University Medical Center	Seoul
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Maasland Hospital	Sittard
Netherlands	Diakonessenhuis Utrecht	Utrecht
Poland	Medical University of Gdansk	Gdansk
Poland	Oncologic Center	Gliwice
Poland	Medical University	Poznan
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Portugal	Hospitais da Universidade de Coimbra (HUC)	Coimbra
Portugal	Instituto Portugues de Oncologia, Centro Regional de Coimbra	Coimbra
Portugal	Maternidade Byssaia Barreto	Coimbra
Portugal	Hospital Distrital De Faro	Faro
Portugal	University Hospital of Santa Maria	Lisboa
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.	Lisbon
Russian Federation	Moscow Oncology Hospital	Moscow
Russian Federation	P.A. Hertzen Research Oncology Institute	Moscow
Singapore	Johns Hopkins Singapore International Medical Centre	Singapore
South Africa	Groote Schuur Hospital	Cape Town
South Africa	Parklands Hospital	Durban
South Africa	Medical Oncology Centre of Rosebank	Johannesburg
South Africa	Sandton Oncology Centre	Johannesburg
South Africa	Pretoria - East Hospital	Lynnwood
Spain	Hospital De La Ribera	Alzira
Spain	Hospital Del Mar	Barcelona
Spain	Hospital Universitario San Cecilio de Granada	Granada
Spain	Hospital General Universitario De Guadalajara	Guadalajara
Spain	Hospital Juan Ramon Jimenez	Huelva
Spain	Hospital Cuidad de Jaen	Jaen
Spain	Centro Oncologico De Galicia Jose Antonio Quirogay Pineyro	La Coruna
Spain	Hospital Universitario Canarias	La Laguna
Spain	Hospital Insular de Gran Canaria	Las Palmas
Spain	Hospital de Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria
Spain	Hospital de la Princesa	Madrid
Spain	Complejo Hospitalario Santa Maria	Orense
Spain	Complejo Hospitalario de Pontevedra	Pontevedra
Spain	Consorci Hospitalari del Parc Tauli	Sabadell
Spain	Hospital Universitario Nuestra Senora de la Candelaria	Santa Cruz de Tenerife
Spain	Hospital Universidad Virgen Del Rocio	Sevilla
Spain	Hospital Virgen Del La Salud	Toledo
Spain	Hospital General Universitario Valencia	Valencia
Spain	Complexo Hospitalario Xeral de Vigo	Vigo Pontevedra
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	University Hospital of Linkoping	Linkoping
Sweden	University Hospital of Malmoe	Malmo
Sweden	Sahlgrenska University Hospital - Molndal at Gothenburg University	Molndal
Sweden	Karolinska University Hospital - Huddinge	Stockholm
Sweden	Umea Universitet	Umea
Sweden	Uppsala University Hospital	Uppsala
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Inselspital Bern	Bern
Switzerland	Spitaeler Chur AG	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	UniversitaetsSpital Zuerich	Zurich
Thailand	Chulalongkorn University Hospital	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
United Kingdom	Bradford Hospitals NHS Trust	Bradford	England
United Kingdom	Broomfield Hospital	Chelmsford, Essex	England
United Kingdom	Saint Margaret's Hospital	Epping Essex	England
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Princess Royal Hospital	Hull	England
United Kingdom	Cookridge Hospital at Leeds Teaching Hospital NHS Trust	Leeds	England
United Kingdom	Imperial College of Medicine	London	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Airedale General Hospital	West Yorkshire	England
United Kingdom	Southend NHS Trust Hospital	Westcliff-On-Sea	England

Sponsors (5)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Breast International Group, Canadian Cancer Trials Group, European Organisation for Research and Treatment of Cancer - EORTC, International Breast Cancer Study Group

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Croatia,  Denmark,  France,  Germany,  Greece,  Guatemala,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Thailand,  United Kingdom, 

References & Publications (10)

Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Rueschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B. Disease-free survival according to degree of HER2 amplification for patients — View Citation

Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Prit — View Citation

Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008 Aug;8(4):324-33. doi: 10.3816/CBC.2008.n.037. Review. — View Citation

McCaskill-Stevens W, Procter M, Goodbrand J, et al.: Disease-free survival according to local immunohistochemistry for HER2 and central fluorescence in situ hydridization for patients treated with adjuvant chemotherapy with and without trastuzumab in the

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohris — View Citation

Procter M, Suter TM, de Azambuja E, Dafni U, van Dooren V, Muehlbauer S, Climent MA, Rechberger E, Liu WT, Toi M, Coombes RC, Dodwell D, Pagani O, Madrid J, Hall M, Chen SC, Focan C, Muschol M, van Veldhuisen DJ, Piccart-Gebhart MJ. Longer-term assessment — View Citation

Shiroiwa T, Fukuda T, Shimozuma K, Ohashi Y, Tsutani K. The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data. Breast Cancer Res Treat. 2008 Jun;109(3):559-66. Epub 2007 Jul 28. — View Citation

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira — View Citation

Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ. Trastuzumab-associated ca — View Citation

Untch M, Gelber RD, Jackisch C, Procter M, Baselga J, Bell R, Cameron D, Bari M, Smith I, Leyland-Jones B, de Azambuja E, Wermuth P, Khasanov R, Feng-Yi F, Constantin C, Mayordomo JI, Su CH, Yu SY, Lluch A, Senkus-Konefka E, Price C, Haslbauer F, Suarez S — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival			No
Primary	Relapse-free survival			No
Primary	Distant disease-free survival			No
Primary	Incidence of cardiac dysfunction			No
Primary	Safety and tolerability			Yes
Secondary	Overall survival			No
Secondary	Time to recurrence			No
Secondary	Time to distant recurrence			No