A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01966471
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This two-arm, randomized, open-label, multicenter study will evaluate the efficacy and safety of trastuzumab emtansine in combination with pertuzumab versus trastuzumab in combination with pertuzumab and a taxane as adjuvant therapy in participants with human epidermal growth (HER) factor 2 (HER2)-positive primary invasive breast cancer. Following surgery and anthracycline-based chemotherapy, participants will receive either trastuzumab emtansine at a dose of 3.6 milligrams per kilogram (mg/kg) and pertuzumab at a dose of 420 milligrams (mg) intravenously (IV) every 3 weeks (q3w) or trastuzumab at a dose of 6 mg/kg and pertuzumab at a dose of 420 mg IV q3w in combination with a taxane.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1846
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
- Non-metastatic histologically confirmed primary invasive breast carcinoma that was operable
- HER2-positive breast cancer
- Known hormone receptor status of the primary tumor
- Adequately excised: participants must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
- Pathological tumor-node-metastasis staging (Union for International Cancer Control-American Joint Committee on Cancer [UICC/AJCC] 7th edition): eligible participants must have either:
Node-positive disease (pN more than or equal to [>/=] 1), any tumor size except T0, and any hormonal receptor status; or Node-negative disease (pN0) with pathologic tumor size >2.0 centimeters by standard local assessment and negative for estrogen receptor (ER) and progesterone receptor (PR) determined by a central pathology laboratory
- Participants with synchronous bilateral invasive disease are eligible only if both lesions are HER2-positive
- No more than 9 weeks (63 days) may elapse between definitive breast surgery (or the last surgery if additional resection required for breast cancer) and randomization
- Baseline left ventricular ejection fraction (LVEF) >/=55% measured by echocardiogram (ECHO; preferred) or multiple-gated acquisition (MUGA) scans
- Documentation on hepatitis B virus (HBV) and hepatitis C virus (HCV) serology is required
- Female participants of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception. For male participants with partners of childbearing potential, one highly effective form of contraception or two effective forms of contraception must be used. Contraception must continue for the duration of study treatment and for 6 months after the last dose of study treatment
- History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
- History of non-breast malignancies within the 5 years prior to randomization, except for carcinoma in situ (CIS) of the cervix, CIS of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
- Any clinical T4 tumor as defined by tumor-node-metastasis classification in UICC/AJCC 7th edition, including inflammatory breast cancer
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (for example, neoadjuvant or adjuvant), including but not limited to, chemotherapy, anti-HER2 therapy (for example, trastuzumab, trastuzumab emtansine, pertuzumab, lapatinib, neratinib, or other tyrosine kinase inhibitors), hormonal therapy, OR anti-cancer radiation therapy (RT) (intra-operative radiotherapy as a boost at the time of primary surgery is acceptable)
- Previous therapy with anthracyclines, taxanes, or HER2-targeted therapy for any malignancy
- History of DCIS and/or lobular CIS (LCIS) that was treated with any form of systemic chemotherapy, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed. Participants who had their DCIS/LCIS treated with surgery only and/or contralateral DCIS treated with radiation are allowed to enter the study
- Participants with contraindication to RT while adjuvant RT is clinically indicated
- Concurrent anti-cancer treatment in another investigational trial
- Cardiopulmonary dysfunction as defined by protocol: angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease, significant symptoms (Grade >/=2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia, myocardial infarction within 12 months prior to randomization, uncontrolled hypertension, evidence of transmural infarction on electrocardiogram (ECG), requirement for oxygen therapy
- Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes, or known infection with HIV
- Any known active liver disease. For participants who are known carriers of HBV/HCV, active hepatitis B/C infection must be ruled out per local guidelines
- Inadequate hematologic, renal or liver function
- Pregnant or lactating women
- Hypersensitivity to any of the study medications or any of the ingredients or excipients of these medications, including hypersensitivity to benzyl alcohol
- Chronic immunosuppressive therapies, including systemic corticosteroids
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Trastuzumab Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Paclitaxel Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Doxorubicin Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Pertuzumab Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Epirubicin Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Docetaxel Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane Cyclophosphamide Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane 5-Fluorouracil Trastuzumab and pertuzumab will be administered concurrently for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) with the taxane (docetaxel or paclitaxel) component of chemotherapy following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab Trastuzumab Emtansine Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab Epirubicin Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab Doxorubicin Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab Cyclophosphamide Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy. Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab 5-Fluorouracil Trastuzumab emtansine and pertuzumab will continue for up to a total duration of 1 year (up to 18 cycles \[1 Cycle = 21 days\]) following anthracycline \[5 fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC) or doxorubicin and cyclophosphamide (AC)\] based chemotherapy.
- Primary Outcome Measures
Name Time Method Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above. IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer \[bc\] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site \[other than the three sites mentioned above\]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population was estimated using the Kaplan-Meier method and estimated the probability of a participant being event-free after 3 years after randomization.
Invasive Disease-Free Survival (IDFS) in the Overall Population First participant randomized up to approximately 7.5 years IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer \[bc\] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site \[other than the three sites mentioned above\]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) First participant randomized up to approximately 7.5 years OS was defined as the time from randomization to death due to any cause.
IDFS Plus Second Primary Non-Breast Cancer Baseline up to approximately 70 months IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site).
Disease-Free Survival (DFS) Baseline up to approximately 70 months DFS was defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS).
Distant Recurrence-Free Interval (DRFI) Baseline up to approximately 70 months DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence.
Percentage of Participants With Adverse Events From randomization to approximately 7.5 years An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0).
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time First participant randomized up to approximately 7.5 years. LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18 The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 7 - 15 points considered to be a clinically meaningful detioration to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18 EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30. There are 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 averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated improvement in quality of life (QOL) while negative change from baseline indicated a deterioration. For symptom scales, positive change from baseline indicated deterioration and negative change indicated improvement.
Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment From start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above. The time to clinically meaningful deterioration in the global health status/Quality of life and Functional (Physical, Role, and Cognitive) subscales of the the QLQ-C30 was assessed from the time of the HER2-Targeted treatment to the worsening in the respective scales. Clinically meaningful deterioration is defined as a decrease in score of 10 points in Physical functioning and HRQoL; decrease of 7 points in Cognitive functioning, and decrease of 14 points in Role functioning.
Trial Locations
- Locations (295)
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Niigata Cancer Ctr Hospital; Breast Surgery
🇯🇵Niigata, Japan
National Hospital Organization Osaka National Hospital; Breast Surgery
🇯🇵Osaka, Japan
Shizuoka Cancer Center; Breast Surgery
🇯🇵Shizuoka, Japan
Jichi Medical University; Breast Oncology
🇯🇵Tochigi, Japan
National Cancer Center Hospital; Medical Oncology
🇯🇵Tokyo, Japan
Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer
🇳🇴Stavanger, Norway
The Cancer Inst. Hosp. of JFCR; Breast Oncology Center
🇯🇵Tokyo, Japan
Fundacion Rodolfo Padilla Padilla A.C.
🇲🇽León, Mexico
Tokyo Medical Uni. Hospital; Breast Oncology
🇯🇵Tokyo, Japan
Hospital San Jose Del Tec. de Monterrey; Oncology
🇲🇽Monterrey, Mexico
Cluj Clinical County Hospital; Oncology Dept
🇷🇴Cluj-Napoca, Romania
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
🇷🇺Moscow, Russian Federation
Instituto Nacional De Cancerologia; Oncology; Tumores Mamarios
🇲🇽Distrito Federal, Mexico
Centro Hemato Oncologico Panama
🇵🇦Panama, Panama
Clinica San Borja
🇵🇪Lima, Peru
Prof. Dr. I. Chiricuta Institute of Oncology
🇷🇴Cluj Napoca, Romania
Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
🇵🇱Bialystok, Poland
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
🇵🇱Kraków, Poland
Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
🇵🇱Gdansk, Poland
Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
🇵🇱Warszawa, Poland
State Medical Academy; Oncology
🇺🇦Dnipropetrovsk, Ukraine
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii; Poradnia Chemioterapii
🇵🇱Lodz, Poland
Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
🇷🇺Kazan, Russian Federation
National University Hospital; National University Cancer Institute, Singapore (NCIS)
🇸🇬Singapore, Singapore
SBI of Healthcare Samara Regional Clinical Oncology Dispensary
🇷🇺Samara, Russian Federation
Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
🇨🇳Kaohsiung, Taiwan
National Taiwan Uni Hospital; General Surgery
🇨🇳Taipei, Taiwan
Taichung Veterans General Hospital; Dept of Surgery
🇨🇳Taichung, Taiwan
Chiang Rai Prachanukroh Hospital; Department Of Medicine
🇹ðŸ‡Chiang Rai, Thailand
Tri-Service General Hospital, Division of General Surgery
🇨🇳Taipei, Taiwan
Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
🇹ðŸ‡Bangkok, Thailand
Buddhachinaraj Phitsanulok Hospital; Chemotherapy Unit ; Department of Medicine
🇹ðŸ‡Phitsanuok, Thailand
Lviv State Oncological Regional Treatment and Diagnostic Center
🇺🇦Lviv, Ukraine
Kaiser Permanente - San Leandro
🇺🇸San Leandro, California, United States
Henry Ford Hospital; Hematology Oncology
🇺🇸Detroit, Michigan, United States
Karmanos Cancer Institute..
🇺🇸Detroit, Michigan, United States
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
🇮🇹Rozzano, Lombardia, Italy
Queen Alexandra Hospital; Portsmouth Haematology & Oncology Centre, Level B
🇬🇧Portsmouth, United Kingdom
Dana Farber Cancer Inst.
🇺🇸Boston, Massachusetts, United States
Kaiser Permanente - San Jose
🇺🇸San Jose, California, United States
Anne Arundel Health System Research Instit-Annapolis Oncology Ctr
🇺🇸Annapolis, Maryland, United States
Sault Area Hospital
🇨🇦Sault Ste. Marie, Ontario, Canada
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Kaiser Permanente - Oakland
🇺🇸Oakland, California, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Southern California Kaiser Permanente
🇺🇸San Diego, California, United States
UC Davis Cancer Center; Oncology
🇺🇸Sacramento, California, United States
Kaiser Permanente - South SF; Oncology Clinical trials
🇺🇸South San Francisco, California, United States
Florida Cancer Specialists; Saint Petersburg
🇺🇸Saint Petersburg, Florida, United States
Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Burnside War Memorial Hospital, Clinical Trials Centre
🇦🇺Adelaide, South Australia, Australia
Indiana University
🇺🇸Indianapolis, Indiana, United States
Calvary Mater Newcastle; Medical Oncology
🇦🇺Waratah, New South Wales, Australia
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
US oncology research at Minnesota Oncology
🇺🇸Saint Paul, Minnesota, United States
Beth Israel Deaconess Med Ctr
🇺🇸Boston, Massachusetts, United States
Mercy Medical Research Institute
🇺🇸Springfield, Missouri, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Dartmouth Hitchcock Med Center
🇺🇸Lebanon, New Hampshire, United States
The Center for Cancer and Blood Disorders - Fort Worth
🇺🇸Fort Worth, Texas, United States
Haematology & Oncology Clinics of Australia Research Centre
🇦🇺South Brisbane, Queensland, Australia
St John of God Murdoch Hospital; Oncology West
🇦🇺Murdoch, Western Australia, Australia
Magee-Woman's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Mercy Clinic Oklahoma Communties, Inc
🇺🇸Oklahoma City, Oklahoma, United States
Cone Health Cancer Center
🇺🇸Greensboro, North Carolina, United States
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
🇧🇷Goiania, GO, Brazil
Hospital Sirio Libanes; Centro de Oncologia
🇧🇷Sao Paulo, SP, Brazil
Memorial Sloan-Kettering Cancer Center
🇺🇸Commack, New York, United States
Sint Augustinus Wilrijk, Apotheek
🇧🇪Wilrijk, Belgium
Wellmont Medical Associates
🇺🇸Bristol, Virginia, United States
ProHEALTH Care Associates LLP
🇺🇸Lake Success, New York, United States
Clinic of Oncology, University Clinical Center Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Regional health authority A vitalite health network
🇨🇦Moncton, New Brunswick, Canada
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Tom Baker Cancer Centre-Calgary
🇨🇦Calgary, Alberta, Canada
Southlake Regional Health Center; Community Care Clinic / Oncology
🇨🇦Newmarket, Ontario, Canada
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, SP, Brazil
Queen Elizabeth II Health Sciences Centre; Oncology
🇨🇦Halifax, Nova Scotia, Canada
Lions Gate Hospital
🇨🇦North Vancouver, British Columbia, Canada
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
London Regional Cancer Centre
🇨🇦London, Ontario, Canada
Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre
🇨🇦Mississauga, Ontario, Canada
Lakeridge Health Oshawa; Oncology
🇨🇦Oshawa, Ontario, Canada
Instituto Oncologico del sur
🇨🇱Temuco, Chile
Windsor Regional Cancer Centre
🇨🇦Windsor, Ontario, Canada
Centre Leon Berard; Departement Oncologie Medicale
🇫🇷Lyon, France
North York General Hospital
🇨🇦Toronto, Ontario, Canada
ONCOCENTRO APYS; OncologÃa
🇨🇱Vina Del Mar, Chile
Cite de La Sante de Laval; Hemato-Oncologie
🇨🇦Laval, Quebec, Canada
Masarykuv onkologicky ustav
🇨🇿Brno, Czechia
McGill University; Glen Site; Oncology
🇨🇦Montreal, Quebec, Canada
Hospital Diagnostico Escalón
🇸🇻San Salvador, El Salvador
Centre Francois Baclesse; Oncologie
🇫🇷Caen, France
HOPITAL JEAN MINJOZ; Oncologie
🇫🇷Besancon, France
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
Centre Eugene Marquis; Service d'oncologie
🇫🇷Rennes, France
HOPITAL TENON; Cancerologie Medicale
🇫🇷Paris, France
Oncomedica S.A.
🇨🇴Monteria, Colombia
Clinique Victor Hugo; Chimiotherapie
🇫🇷Le Mans, France
Institut Bergonie; Oncologie
🇫🇷Bordeaux, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut de cancerologie du Gard
🇫🇷Nimes, France
Clinique Sainte Catherine
🇫🇷Avignon, France
CHU de Brest - Hôpital de Morvan
🇫🇷Brest, France
Centre Oscar Lambret; Cancerologie Gynecologique
🇫🇷Lille, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Centre Armoricain de Radiotherapie, de Imagerie Medicale et de Oncologie (CARIO)
🇫🇷Plerin, France
Centre D'Oncologie de Gentilly; Oncology
🇫🇷Nancy, France
Institut De Cancerologie De La Loire; Consult Oncologie Niveau 0
🇫🇷St Priest En Jarez, France
Institut d'oncologie de l'Orangerie; Chimiotherapie
🇫🇷Strasbourg, France
Centre Paul Strauss; Oncologie Medicale
🇫🇷Strasbourg, France
Institut Claudius Regaud; Departement Oncologie Medicale
🇫🇷Toulouse, France
LTD Institute of Clinical Oncology
🇬🇪Tbilisi, Georgia
Khechinashvili University Hospital ;Breast Unit
🇬🇪Tbilisi, Georgia
Centre Alexis Vautrin; Oncologie Medicale
🇫🇷Vandoeuvre-les-nancy, France
Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
🇩🇪Hannover, Germany
Städtische Kliniken Frankfurt am Main Höchst
🇩🇪Frankfurt, Germany
Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Lübeck, Germany
Klinikum Kulmbach; Frauenklinik
🇩🇪Kulmbach, Germany
Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche
🇩🇪Berlin, Germany
Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Hannover, Germany
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
🇩🇪Freiburg, Germany
Grupo Angeles
🇬🇹Guatemala City, Guatemala
Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH
🇩🇪Georgsmarienhütte, Germany
Dres.Jochen Wilke und Harald Wagner
🇩🇪Fürth, Germany
Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika
ðŸ‡ðŸ‡ºDebrecen, Hungary
Klinikum Meiningen Klinik f.Gynäkologie und Geburtshilfe
🇩🇪Meiningen, Germany
GRN-Klinik Weinheim; Abt.Gynäkologie und Geburtshilfe
🇩🇪Weinheim, Germany
Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
ðŸ‡ðŸ‡ºBudapest, Hungary
Istituto Nazionale Tumori Regina Elena IRCCS
🇮🇹Roma, Lazio, Italy
Sourasky / Ichilov Hospital; Oncology Department
🇮🇱Tel Aviv, Israel
Gunma Prefectural Cancer Center; Breast Oncology
🇯🇵Gunma, Japan
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
🇮🇹Aviano, Friuli-Venezia Giulia, Italy
ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit
🇮🇹Cremona, Lombardia, Italy
Humanitas Centro Catanese Di Oncologia; Oncologia Medica
🇮🇹Misterbianco (CT), Sicilia, Italy
Nagoya City University Hospital; Breast Surgery
🇯🇵Aichi, Japan
Hiroshima University Hospital; Breast Surgery
🇯🇵Hiroshima, Japan
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera S. Maria - Terni; Oncologia
🇮🇹Terni, Umbria, Italy
Gunma University Hospital; Department of Breast and Endocrine Surgery
🇯🇵Gunma, Japan
Hiroshima City Hiroshima Citizens Hospital; Breast Surgery
🇯🇵Hiroshima, Japan
ASST DI MONZA; Oncologia Medica
🇮🇹Monza, Lombardia, Italy
Ospedale Misericordia E Dolce; Oncologia Medica
🇮🇹Prato, Toscana, Italy
Aichi Cancer Center Hospital, Breast Oncology
🇯🇵Aichi, Japan
Hyogo College Of Medicine; Breast And Endocrine Surgery
🇯🇵Hyogo, Japan
Ospedale Antonio Perrino; Oncologia Medica
🇮🇹Brindisi, Puglia, Italy
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
🇮🇹Padova, Veneto, Italy
Iwate Med Univ School of Med; Surgery
🇯🇵Iwate, Japan
Kumamoto City Hospital, Breast and Endocrine Surgery
🇯🇵Kumamoto, Japan
Kawasaki Medical School Hospital; Breast and Thyroid Surgery
🇯🇵Okayama, Japan
St. Luke's Internat. Hospital, Breast Surgical Oncology
🇯🇵Tokyo, Japan
Saitama Cancer Center, Breast Oncology
🇯🇵Saitama, Japan
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
🇰🇷Seoul, Korea, Republic of
Tokai University Hospital, Breast Surgery
🇯🇵Kanagawa, Japan
Osaka International Cancer Institute; Breast and Endocrine Surgery
🇯🇵Osaka, Japan
Saitama Medical University International Medical Center; Breast Oncology
🇯🇵Saitama, Japan
Shizuoka General Hospital; Breast Surgery
🇯🇵Shizuoka, Japan
Tokyo Metropolitan; Komagome Hospital, Surgery
🇯🇵Tokyo, Japan
Showa University Hospital; Breast Surgery
🇯🇵Tokyo, Japan
Clinica de Especialidades Medicas
🇵🇪Lima, Peru
San Juan de Dios Hospital;Oncology Unit
🇵ðŸ‡Pasay, Philippines
Regional Institute of Oncology Iasi
🇷🇴Iasi, Romania
Oslo universitetssykehus HF, Ullevål, Kreftsenteret
🇳🇴Oslo, Norway
Institutul Oncologic Prof. Dr. Al. Trestioreanu Bucuresti
🇷🇴Bucuresti, Romania
Instituto Oncologico Miraflore
🇵🇪Miraflores, Peru
Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii
🇵🇱Bydgoszcz, Poland
State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
🇷🇺Orenburg, Russian Federation
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸Malaga, Spain
National Cancer Centre; Medical Oncology
🇸🇬Singapore, Singapore
Sahlgrenska Universitetssjukhuset; Jubileumskliniken
🇸🇪Göteborg, Sweden
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
🇪🇸Murcia, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
🇪🇸Madrid, Spain
Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
🇨ðŸ‡Chur, Switzerland
Akademiska sjukhuset, Onkologkliniken
🇸🇪Uppsala, Sweden
Luzerner Kantonsspital; Medizinische Onkologie
🇨ðŸ‡Luzern, Switzerland
Hospital ClÃnico Universitario de Valencia; Servicio de OncologÃa
🇪🇸Valencia, Spain
Changhua Christian Hospital; Dept of Surgery
🇨🇳Changhua, Taiwan
Universitetssjukhuset Örebro, Onkologiska kliniken
🇸🇪Örebro, Sweden
VETERANS GENERAL HOSPITAL; Department of General Surgery
🇨🇳Taipei, Taiwan
Freeman Hospital; Northern Centre For Cancer Care
🇬🇧New Castle Upon Tyne, United Kingdom
Peterborough City Hospital, Edith Cavell Campus; Oncology Department
🇬🇧Peterborough, United Kingdom
Royal Marsden Hospital - Fulham; Oncology Department
🇬🇧London, United Kingdom
Cheltenham General Hospital; Gloucestershire Oncology Centre
🇬🇧Cheltenham, United Kingdom
Leicester Royal Infirmary; Dept. of Medical Oncology
🇬🇧Leicester, United Kingdom
Chulalongkorn Hospital; Medical Oncology
🇹ðŸ‡Bangkok, Thailand
Velindre Cancer Centre; Oncology Dept
🇬🇧Cardiff, United Kingdom
Western General Hospital; Edinburgh Breast Unit
🇬🇧Edinburgh, United Kingdom
Maidstone Hospital; Kent Oncology Centre
🇬🇧Maidstone, United Kingdom
Christie Hospital; Breast Cancer Research Office
🇬🇧Manchester, United Kingdom
Royal Cornwall Hospital; Dept of Clinical Oncology
🇬🇧Cornwall, United Kingdom
University Hospital Coventry; InHANSE Unit and Clinical Trials Cancer Treatment Centre
🇬🇧Coventry, United Kingdom
Royal Devon & Exeter Hospital; Oncology Centre
🇬🇧Exeter, United Kingdom
Mount Vernon Cancer Centre
🇬🇧Northwood, United Kingdom
Royal Surrey County Hospital; St. Lukes Cancer Centre
🇬🇧Guildford, United Kingdom
Nottingham City Hospital; Oncology
🇬🇧Nottingham, United Kingdom
Yeovil District Hospital; Macmillan Cancer Unit
🇬🇧Yeovil, United Kingdom
Hospital de Cancer de Barretos
🇧🇷Barretos, SP, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Hospital Perola Byington
🇧🇷Sao Paulo, SP, Brazil
Hospital Paulistano
🇧🇷Sao Paulo, SP, Brazil
National Cancer Center; Medical Oncology
🇰🇷Gyeonggi-do, Korea, Republic of
Ajou Uni Hospital; Medical Oncology
🇰🇷Gyeonggi-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
🇩🇪Hamburg, Germany
AGAPLESION Markus-Krankenhaus
🇩🇪Frankfurt, Germany
Klinikum Augsburg
🇩🇪Augsburg, Germany
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
🇩🇪Dresden, Germany
Hochwaldkrankenhaus
🇩🇪Bad Nauheim, Germany
Praxis Dr.med. Katja Ziegler-Löhr
🇩🇪Köln, Germany
Hämatologisch/Onkologische Praxis Prof. Dr. Decker, Studienzentrum
🇩🇪Ravensburg, Germany
Agaplesion Diakonieklinikum Rotenburg
🇩🇪Rotenburg/Wümme, Germany
Klinikum der Universität München; Campus Großhadern; Klinik und Poliklinik für Frauenheilkunde
🇩🇪Muenchen, Germany
Dres. Helmut Forstbauer, Carsten Ziske und Kollegen; Onkologische Schwerpunktpraxis
🇩🇪Troisdorf, Germany
Klinikum Worms; Frauenklinik; Klinik für Gynäkologie und Geburtshilfe
🇩🇪Worms, Germany
Hospital de Cruces; Servicio de Oncologia
🇪🇸Bilbao, Vizcaya, Spain
Hospital Universitario de Canarias;servicio de Oncologia
🇪🇸La Laguna, Tenerife, Spain
Hospital del Mar; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Duran i Reynals; Oncologia
🇪🇸Barcelona, Spain
Kaiser Permanente - Walnut Creek; Oncology Pharmacy
🇺🇸Walnut Creek, California, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
University Cancer & Blood Center, LLC; Research
🇺🇸Athens, Georgia, United States
Quincy Medical Group; Canc Ctr at Blessing Hosp
🇺🇸Quincy, Illinois, United States
Central Georgia Cancer Care PC
🇺🇸Macon, Georgia, United States
University of Virginia Health System; Hematology/Oncology Division
🇺🇸Charlottesville, Virginia, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Washington
🇺🇸Seattle, Washington, United States
Florida Cancer Specialists; SCRI
🇺🇸Fort Myers, Florida, United States
Samsung Medical Centre; Division of Hematology/Oncology
🇰🇷Seoul, Korea, Republic of
Natl Hosp Org Shikoku; Cancer Ctr, Surgery
🇯🇵Ehime, Japan
National Hospital Organization Kyushu Cancer Center;Breast Oncology
🇯🇵Fukuoka, Japan
SCRI Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Kumamoto Shinto General Hospital; Breast Cancer Center
🇯🇵Kumamoto, Japan
Kyoto University Hospital; Breast Surgery
🇯🇵Kyoto, Japan
Naha-nishi Clinic; Surgery
🇯🇵Okinawa, Japan
Kaiser Permanente - Sacramento; Oncology Pharmacy
🇺🇸Sacramento, California, United States
Kaiser Permanente - Roseville; Oncology Pharmacy
🇺🇸Roseville, California, United States
Kaiser Permanente - Vallejo
🇺🇸Vallejo, California, United States
Thompson Cancer Survival Center
🇺🇸Knoxville, Tennessee, United States
Virginia Commonwealth University - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Blue Ridge Cancer Care - Salem
🇺🇸Salem, Virginia, United States
Epworth HealthCare; Clinical Trials Centre
🇦🇺Richmond, Victoria, Australia
Hopital du Saint Sacrement
🇨🇦Quebec City, Quebec, Canada
MULTISCAN, s.r.o., Radiologicke centrum Pardubice
🇨🇿Pardubice, Czechia
Ico - Paul Papin
🇫🇷Angers, France
Centre Jean Perrin; Oncologie
🇫🇷Clermont Ferrand, France
Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology
🇨🇿Hradec Kralove, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Polyclinique De Courlancy; Centre Radiotherapie Oncologie
🇫🇷Reims, France
Gemeinschaftspraxis Dr. Bueckner und Dr. Nueckel
🇩🇪Bochum, Germany
Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher
🇩🇪Stralsund, Germany
Princess Margaret Hospital; Oncology
ðŸ‡ðŸ‡°Hong Kong, Hong Kong
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
ðŸ‡ðŸ‡ºSzeged, Hungary
Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
🇮🇹Milano, Lombardia, Italy
Consultorio de Medicina Especializada; Dentro de Condominio San Francisco
🇲🇽Mexico City, Mexico
East Avenue Medical Center
🇵ðŸ‡Quezon City, Philippines
Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
🇵🇱Otwock, Poland
Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii
🇵🇱Lublin, Poland
Clinica Internacional, Sede San Borja; Unidad de Investigacion de ClÃnica Internacional
🇵🇪Lima, Peru
SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF
🇷🇺Ryazan, Russian Federation
Scientific Research Institute n.a. N.N. Petrov
🇷🇺Saint Petersburg, Russian Federation
Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich
🇨ðŸ‡Zürich, Switzerland
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Musgrove Park Hospital; Department Clinical Research, Beacon Centre
🇬🇧Somerset, United Kingdom
Weston Park Hospital; Cancer Clinical Trials Centre
🇬🇧Sheffield, United Kingdom
Royal Marsden Hospital; Dept of Medical Oncology
🇬🇧Sutton, United Kingdom
Uni Hospital of North Staffordshire; Staffordshire Oncology Centre
🇬🇧Stoke-on-Trent, United Kingdom
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
🇺🇸Nashville, Tennessee, United States
Chemotherapy and Immunotherapy Clinic Medulla
🇬🇪Tbilisi, Georgia
Chaim Sheba Medical Center; Oncology Dept
🇮🇱Ramat Gan, Israel
Sagara Hospital; Breast Surgery
🇯🇵Kagoshima, Japan
St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery
🇯🇵Kanagawa, Japan
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
Frankston Hospital; Oncology/Haematology
🇦🇺Frankston, Victoria, Australia
Municipal Hospital of Uzsoki Utca; Centre of Oncoradiology
ðŸ‡ðŸ‡ºBudapest, Hungary
University Clinical Center of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
Centro Oncológico Sixtino / Centro Oncológico SA
🇬🇹Guatemala, Guatemala
BC Cancer - Kelowna (Sindi Ahluwalia Hawkins Centre)
🇨🇦Kelowna, British Columbia, Canada
West Clinic
🇺🇸Germantown, Tennessee, United States
Austin Hospital; Medical Oncology
🇦🇺Heidelberg, Victoria, Australia
Charing Cross Hospital
🇬🇧London, United Kingdom
Queen Mary Hospital; Dept of Surgery
ðŸ‡ðŸ‡°Pokfulam, Hong Kong
Tuen Mun Hospital; Clinical Oncology
ðŸ‡ðŸ‡°Hong Kong, Hong Kong