A Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT02131064
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This is a randomized, multicenter, open-label, two-arm study in treatment-naive participants with operable, locally advanced, or inflammatory, centrally-assessed HER2-positive early breast cancer (EBC) whose primary tumors were greater than or equal to (\>/=) 2 centimeters (cm). The study was designed to evaluate the efficacy and safety of trastuzumab emtansine + pertuzumab (experimental arm; T-DM1 + P) versus chemotherapy, trastuzumab + pertuzumab (control arm; TCH + P). The study comprised a neoadjuvant treatment period, followed by surgery, and an adjuvant treatment period.
Treatment can be stopped due to disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 444
- Histologically confirmed invasive breast cancer with a primary tumor size of greater than (>) 2 cm
- HER2-positive breast cancer
- Participants with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) are eligible provided all discrete lesions are sampled and centrally confirmed as HER2 positive
- Stage at presentation: cT2-cT4, cN0-cN3, cM0, according to American Joint Committee on Cancer (AJCC) staging system
- Known hormone receptor status of the primary tumor
- Participant agreement to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Baseline Left Ventricular Ejection Fraction (LVEF) >/= 55 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
- Effective contraception as defined by protocol
- Stage IV (metastatic) breast cancer
- Participants who have received prior anti-cancer therapy for breast cancer except those participants with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from surgery until diagnosis of current breast cancer
- Participants with multicentric (multiple tumors involving more than 1 quadrant) or bilateral breast cancer
- Participants who have undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
- Axillary lymph node dissection or positive sentinel lymph node prior to start of neoadjuvant therapy
- History of concurrent or previously non-breast malignancies except for appropriately treated (1) non-melanoma skin cancer and (2) in situ carcinomas, including cervix, colon, and skin. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease-free >/= 5 years
- Treatment with any investigational drug within 28 days prior to randomization
- Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0
- Any significant concurrent medical or surgical conditions or findings that would jeopardize the participant's safety or ability to complete the study
- Current pregnancy or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trastuzumab Emtansine (T-DM1) + Pertuzumab Trastuzumab Emtansine Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period). Trastuzumab (TCH) + Pertuzumab Docetaxel Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Trastuzumab (TCH) + Pertuzumab Carboplatin Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Trastuzumab (TCH) + Pertuzumab Pertuzumab Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Trastuzumab (TCH) + Pertuzumab Trastuzumab Participants will receive pertuzumab 840 milligrams (mg) (loading dose) and 420 mg (maintenance dose) intravenous (IV) infusion followed by trastuzumab 8 milligrams per kilogram (mg/kg) (loading dose) and 6 mg/kg (maintenance dose) IV infusion followed by docetaxel 75 milligrams per square meter (mg/m\^2) IV infusion and carboplatin at a dose to achieve an area under the curve (AUC) of 6 milligrams per milliliter\* minute (mg/mL\*min) IV infusion every 3 weeks (q3w) for 6 cycles in neoadjuvant period. Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab 8 mg/kg (loading dose) and 6 mg/kg (maintenance dose) IV infusion q3w for rest of the cycles (12 cycles) in adjuvant period (up to a total of 18 cycles). Trastuzumab Emtansine (T-DM1) + Pertuzumab Pertuzumab Participants will receive pertuzumab 840 mg (loading dose) and 420 mg (maintenance dose) IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion q3w for a total of 18 cycles (6 cycles of neoadjuvant period and 12 cycles of adjuvant period).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months) tpCR 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 ( that is \[i.e.\], ypT0/is, ypN0 in the American Joint Committee on Cancer \[AJCC\] staging system, 7th edition). Percentage of participants with tpCR was reported.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL.
Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function.
Event-Free Survival From randomization up to disease progression or recurrence or death (up to approximately 47 months) Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS 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 treatment.
Invasive Disease-free Survival (IDFS) From surgery to the first documented occurrence of IDFC event (up to approximately 47 months) IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of 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 treatment.
Percentage of Participants by Response for Skin Problem Single Items Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) Participants answered the Question 1 "Did itching skin bother you?" and Question 2 "Have you had skin problems?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.
Time to Clinically Meaningful Deterioration in GHS/QoL Score From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley.
Maximum Observed Serum Concentration (Cmax) of Trastuzumab 15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period Only participants who received trastuzumab were to be analyzed for this outcome.
Cmin of Trastuzumab Emtansine and Total Trastuzumab Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Percentage of Participants by Response for Neuropathy Single Item Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months) Participants answered the question "Did you have tingling hands/feet?", from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.
Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Overall Survival From randomization until death (up to approximately 47 months) Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 3 years OS 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 treatment.
Percentage of Participants Who Received Breast-Conserving Surgery (BCS) Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period) BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer.
Minimum Observed Serum Concentration (Cmin) of Trastuzumab Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period Only participants who received trastuzumab were to be analyzed for this outcome.
Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1) 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period Percentage of Participants With ATA to Trastuzumab Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period Time to Clinically Meaningful Deterioration in Function Subscale From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley.
Cmax of Trastuzumab Emtansine and Total Trastuzumab 15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period. Only participants who received trastuzumab emtansine were to be analyzed for this outcome.
Percentage of Participants by Response for Hair Loss Single Item Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months) Participants answered the Question "Have you lost any hair?", from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported.
Percentage of Participants With Selected Adverse Events (AEs) Baseline to end of study (approximately 47 months) Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss.
Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1 Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (\>/=) 0.60 titer units higher than the result at baseline.
Trial Locations
- Locations (79)
Cancer Care Assoc Med Group
🇺🇸Los Angeles, California, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Hope A Women's Cancer Center
🇺🇸Asheville, North Carolina, United States
St. Michael'S Hospital
🇨🇦Toronto, Ontario, Canada
St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
🇺🇸Fullerton, California, United States
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
Coastal Integrative Cancer Care
🇺🇸San Luis Obispo, California, United States
Central Coast Medical Oncology
🇺🇸Santa Maria, California, United States
Memorial Cancer Institute
🇺🇸Hollywood, Florida, United States
Comprehensive Cancer Centers of Nevada - Henderson
🇺🇸Henderson, Nevada, United States
Hospital Nuestra Señora de Sonsoles; servicio de Oncologia
🇪🇸Avila, Spain
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Klinikum Sindelfingen-Böblingen; Frauenklinik
🇩🇪Böblingen, Germany
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Cross Cancer Institute ; Dept of Medical Oncology
🇨🇦Edmonton, Alberta, Canada
Universitätsklinikum Mainz
🇩🇪Mainz, Germany
CHD Les Oudairies
🇫🇷La Roche Sur Yon, France
Centre Rene Gauducheau
🇫🇷Saint Herblain, France
Chum Hospital Notre Dame
🇨🇦Montreal, Quebec, Canada
IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia
🇪🇸San Sebastian, Guipuzcoa, Spain
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
🇪🇸Sabadell, Barcelona, Spain
Ico - Paul Papin
🇫🇷Angers, France
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Universitätsklinikum Erlangen; Frauenklinik
🇩🇪Erlangen, Germany
Fundacio Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
HOPITAL JEAN MINJOZ; Oncologie
🇫🇷Besancon, France
Centre Catherine De Sienne
🇫🇷Nantes, France
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Quiron de Madrid; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital del Mar; Servicio de Oncologia
🇪🇸Barcelona, Spain
Complejo Hospitalario de Jaen
🇪🇸Jaen, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitari de Lleida Arnau de Vilanova
🇪🇸Lleida, Lerida, Spain
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
ProHEALTH Care Associates LLP
🇺🇸Lake Success, New York, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre Oscar Lambret
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Luisenkrankenhaus GmbH, Brustzentrum
🇩🇪Düsseldorf, Germany
Interdisziplinäres Onkologisches Zentrum
🇩🇪München, Germany
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Regional Oncology Hospital Of Kursk; Chemotherapy
🇷🇺Kislino, Kursk Region, Russian Federation
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
🇪🇸La Coruña, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Hopital Morvan
🇫🇷Brest, France
Nouvel Hopital Civil - CHU Strasbourg
🇫🇷Strasbourg, France
UZ Antwerpen
🇧🇪Edegem, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Clinique Saint-Joseph
🇧🇪Liège, Belgium
Sint Augustinus Wilrijk
🇧🇪Wilrijk, Belgium
Clinique Ste-Elisabeth, Pharmacie
🇧🇪Namur, Belgium
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
🇨🇳Taipei, Taiwan
S.I. Russian Oncological Research Center n.a. N.N. Blokhin
🇷🇺Moscow, Russian Federation
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
State Inst. Of Healthcare Orenburg Regional Clinical Oncology Dis
🇷🇺Orenburg, Russian Federation
Railway Clinical Hospital on Saratov - 2 Station Oao "Rzhd"
🇷🇺Saratov, Russian Federation
Saint-Petersburg City Clinical Oncology Dispensary
🇷🇺St Petersburg, Russian Federation
National Taiwan Uni Hospital
🇨🇳Taipei City, Taiwan
Cherkassy Regional Oncological Hospital
🇺🇦Cherkassy, Ukraine
Karkiv Regional Oncology Center
🇺🇦Kharkiv, Ukraine
Mackay Memorial Hospital; Dept of Surgery
🇨🇳Taipei, Taiwan
Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
🇨🇳Kaohsiung, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Lvov State Regional Center
🇺🇦Lvov, Ukraine
State Medical Academy; Oncology
🇺🇦Dnipropetrovsk, Ukraine
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY
🇨🇦Quebec, Canada
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
🇪🇸Madrid, Spain
Md Anderson Cancer Center Orlando
🇺🇸Orlando, Florida, United States
Roper Bon Secours St. Francis Cancer Center
🇺🇸Charleston, South Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States