Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer
- Registration Number
- NCT00721409
- Lead Sponsor
- Pfizer
- Brief Summary
The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 177
- Inoperable estrogen receptor positive and HER2 negative breast cancer.
- Postmenopausal status.
- Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory.
- Acceptable bone marrow, liver and kidney function.
- Prior or concomitant treatment for advanced breast cancer.
- Other major cancer in the past 3 years.
- Important cardiovascular events in the past 6 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Arm B letrozole letrozole Arm A PD 0332991 letrozole + PD 0332991 Arm A letrozole letrozole + PD 0332991
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Related Adverse Events at Phase 1 Maximum treatment duration (approximately 55 months) An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1 Maximum treatment duration (approximately 55 months) An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment From randomization date to date of first documentation of progression or death (assessed up to 41 months) PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).
Number of Participants With Dose Limiting Toxicities at Phase 1 Cycle 2 (4 weeks) Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets \<25,000/μL, ANC \<500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count \<50,000/μL; ANC \<1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.
- Secondary Outcome Measures
Name Time Method Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1 From Baseline up to end of study (assessed up to 55 months) Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: AUC24 at Phase 1 Cycle 2 Day 14, Cycle 2 Day 28 On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Overall Survival (OS) at Phase 2 From randomization until death (assessed up to 86 months) Time in weeks or months from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7 or 30.44 if in months.
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1 From Baseline up to end of study (assessed up to 55 months) CBR is defined as a confirmed CR, confirmed PR, or stable disease (SD) for at least 24 weeks on study according to RECIST. Confirmed responses are those that persisted on repeat imaging \>= 4 weeks after initial response.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Terminal Plasma Half-life (t1/2) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Volume of Distribution (Vz/F) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval at Phase 1 Cycle 1 Day 1 prior to dosing, Cycle 1 Day 14 (2, 4 [prior to meal], 8, 24, 48, and 96 hours after dosing of Palbociclib), Cycle 2 Day 1 and Day 14 (prior to and 4 hours after dosing of letrozole) Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Participants with maximum increase from baseline of 30 to less than (\<) 60 msec(borderline) and greater than or equal to (\>=) 60 msec (prolonged) were summarized.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Cmax at Phase 1 Cycle 2 Day 14, and Cycle 2 Day 28 On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Apparent Clearance (CL/F) at Phase 1 Cycle 1 Day 14, and Cycle 2 Day 14 On Cycle 1 Day 14, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, 24, 48, 96 and 120 hours after Palbociclib dosing. On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing.
Summary of Plasma Letrozole Pharmacokinetic Parameter Following Letrozole Alone and in Combination With Palbociclib: Tmax at Phase 1 Cycle 2 Day 14, and Cycle 2 Day 28 On Cycle 2 Day 14, plasma pharmacokinetic samples for Palbociclib and letrozole were collected prior to and 1, 2, 4, 8, 12 and 24 hours after Palbociclib and letrozole dosing. On Cycle 2 Day 28, plasma pharmacokinetic samples were collected prior to and 1, 2, 4, 8, 12, and 24 hours after letrozole dosing.
Objective Response Rate - Percentage of Participants With Confirmed Objective Response in Participants With Measurable Disease at Phase 2- Investigator Assessment From randomization up to the end of treatment (approximately 41 months) Percentage of participants with objective response based assessment of confirmed CR or PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions. Measurable disease referred to the lesions that was accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10-16 mm with spiral computer tomography scan (depending on reconstruction interval). Clinical lesions were only be considered measurable when they were superficial (eg, skin nodules, palpable lymph nodes).
Duration of Response at Phase 2 - Investigator Assessment From randomization up to the end of treatment (approximately 41 months) Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization \[or first dose of study medication for non-randomized studies\] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\] per RECIST).
Summary of Copy Number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) at Phase 2 Screening visit (≤ 28 Days prior to dosing) Gene copy number for CCND1 (CCND1/CEP11) and p16/INK4A (p16/CEP9) were evaluated. This analysis was done for Phase 2 combined group.
Objective Response Rate - Percentage of Participants With Confirmed Objective Response at Phase 2- Investigator Assessment From randomization up to the end of treatment (approximately 41 months) Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.0: CR defined as disappearance of all target lesions and non-target lesions. PR defined as ≥30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions.
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - p16/INK4A, CCND1 Screening visit (≤ 28 Days prior to dosing) Tissue samples were used for retrospective biomarker analyses. For Phase 2 Part 2, the tissue samples were sent to a central laboratory for the assessment of participant selection biomarkers. For Phase 2 Part 1, the assessment of the biomarkers (CCND1 amplification and/or loss of p16) were performed retrospectively from the available samples.
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Tumor Retinoblastoma (RB) and CyclinD1 Screening visit (≤ 28 Days prior to dosing) Presence or absence of tumor RB and CyclinD1 were evaluated. The following definitions of expression applied in the below table: Positive: any expression \>0 and Negative: any expression=0.
Number of Participants With TEAEs (All Causalities) at Phase 2 Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non-serious AEs.SAE:AE resulting in any of following outcomes/deemed significant and jeopardized participants or required treatment to prevent other AE outcomes for any other reason:death;initial or prolonged inpatient hospitalization;life-threatening experience (immediate risk of dying);persistent or significant disability/incapacity;congenital anomaly.Treatment emergent AEs:events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or worsened relative to pre-treatment state.AEs were graded as per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and coded using Medical Dictionary for Regulatory Activities (MedDRA). Participants with AE of grade 3 or 4 and grade 5 were reported as Grade 3:Severe, Grade 4:Life threatening, Grade 5:Death related to AE.
Number of Participants With CBR at Phase 2 - Investigator Assessment From randomization up to the end of treatment (approximately 41 months) CBR is defined as a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) for at least 24 weeks on study according to RECIST.
Time to Tumor Progression (TTP) at Phase 2-Investigator Assessment From randomization up to the end of treatment (approximately 41 months) Time in weeks, (months or years) from randomization or (start of study treatment for non-randomized studies) to first documentation of objective tumor progression. TTP was calculated as (first event date or last known progression-free date minus the date of randomization \[or first dose of study medication for non-randomized studies\] plus 1) divided by 7 or 30.44 if in months. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\] per RECIST).
Percentage of Participants With Tumor Expression of CYP19A1 and CCND1 Genotypes at Phase 2 Screening visit (≤ 28 Days prior to dosing) One 2-mL blood specimen was collected for the analysis of germline polymorphism in CYP19A1 and CCND1 genes. A single nucleotide polymorphism (SNP) rs4646 as defined in the National Center for Biotechnology Information (NCBI) database in the aromatase gene (CYP19A1) was analyzed. A germline polymorphism G/A870 (rs9344) in the CCND1 gene was analyzed.
Change From Baseline in Modified Brief Pain Inventory in Pain Severity Scale (mBPI-sf) Questionnaire at Phase 2 Baseline, End of treatment (approximately 41 months) The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Change From Baseline in Modified Brief Pain Inventory in Pain Interference Scale (mBPI-sf) Questionnaire at Phase 2 Baseline, End of treatment (approximately 41 months) The mBPI-sf is a validated and reliable self-report questionnaire which consists of 13 questions that assess the severity and impact of pain on daily function. The 13 items of the questionnaire make up two scales and two single items. The scales include the 4-item Pain Severity Scale (worst pain, least pain, average pain, and pain right now) and the 7-item Pain Interference Scale (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each item of the pain severity and pain interference scales are based on a 11-point numeric rating scale from 0 ("no pain" or "does not interfere") to 10 ("pain as bad as you can imagine" or "completely interferes").
Presence or Absence of Tumor Tissue Biomarkers at Phase 2 - Ki67 Screening visit (≤ 28 Days prior to dosing) Frequency of tumor tissue biomarker Ki67 was evaluated in across treatment groups.
Number of Participants With Treatment-Related Adverse Events at Phase 2 Baseline up to 28 days after last dose of study drug (for a maximum of 86 months) AE: any untoward medical occurrence in a participant who received study drug. AEs included both serious and non-serious adverse events. SAE: AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs: events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Treatment related AEs: all AEs with causality related to treatment. Relatedness to drug was assessed by the investigator. AEs were graded according to the CTCAE version 3.0 and coded using the MedDRA. Number of participants with AE of grade 3 or 4 and with AE of grade 5 were reported as Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE.
Trial Locations
- Locations (90)
Central Hematology Oncology Medical group Inc.
🇺🇸Alhambra, California, United States
TORI -US Central Administration (Regulatory Management)
🇺🇸Los Angeles, California, United States
TORI -US Central Administration
🇺🇸Los Angeles, California, United States
UCLA Hematology Oncology-Santa Monica
🇺🇸Santa Monica, California, United States
Illinois Cancer Specialists
🇺🇸Chicago, Illinois, United States
Resurrection Medical Group
🇺🇸Chicago, Illinois, United States
UCLA Hematology/Oncology - Alhambra
🇺🇸Alhambra, California, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
UCLA West Medical Pharmacy (Drug Management Only)
🇺🇸Los Angeles, California, United States
UCLA West Medical Pharmacy
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Drug Management Only: UCLA West Medical Pharmacy
🇺🇸Los Angeles, California, United States
Drug Management Only
🇺🇸Los Angeles, California, United States
Regulatory Managment
🇺🇸Los Angeles, California, United States
TORI Central Administration (Regulatory Management)
🇺🇸Los Angeles, California, United States
TRIO-US Central Administration
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology
🇺🇸Los Angeles, California, United States
TORI Central Administration (Regulatory Managment Only)
🇺🇸Los Angeles, California, United States
UCLA, Hematology/Oncology
🇺🇸Los Angeles, California, United States
Westwood Bowyer Clinic, Peter Morton Medical Building
🇺🇸Los Angeles, California, United States
Central Hematology Oncology Medical Group, Inc
🇺🇸Pasadena, California, United States
Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates
🇺🇸Redondo Beach, California, United States
Sansum Santa Barbara Medical Foundation Clinic
🇺🇸Santa Barbara, California, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Santa Monica-UCLA Medical Center and Orthopaedic Hospital
🇺🇸Santa Monica, California, United States
UCLA Hematology/Oncology - Santa Clarita
🇺🇸Valencia, California, United States
Gwinnett Hospital System Inc.-d/b/a-The Center for Cancer Care
🇺🇸Snellville, Georgia, United States
North Shore Oncology-Hematology Associates
🇺🇸Libertyville, Illinois, United States
North Shore Hematology Oncology
🇺🇸Skokie, Illinois, United States
Texas Oncology-Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Investigational Products Center (IPC)
🇺🇸Fort Worth, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
US Oncology Research and Clinical Pharmacy
🇺🇸Fort Worth, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Woodbridge, Virginia, United States
Gemeinschaftspraxis Haematologie-Onkologie
🇩🇪Dresden, Germany
Fovarosi Onkormanyzat Uzsoki Utcai Korhaz
🇭🇺Budapest, Hungary
Ospedale Civile di Ravenna
🇮🇹Ravenna, Italy
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Eastleigh Breast Care Centre
🇿🇦Pretoria, South Africa
Department of Oncotherapy, National Hospital
🇿🇦Bloemfontein, South Africa
Hospital General Universitario Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Centro Oncologico de Galicia
🇪🇸La Coruña, Spain
Municipal Treatment-and-Prophylactic Institution 'Donetsk City Oncological Dispensary' Radiology dep
🇺🇦Donetsk, Ukraine
Regulatory Office: Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Nationales Centrum fuer Tumorerkrankungen
🇩🇪Heidelberg, Germany
Onkolog. Gemeinschaftspraxis
🇩🇪Muenchen, Germany
Frauenklinik vom Roten Kreuz
🇩🇪Muenchen, Germany
Frauenklinik und Poliklinik Klinikum rechts der Isar, Technische Universitaet Muenchen
🇩🇪Muenchen, Germany
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Universitaetsklinik und Poliklinik fuer Gynaekologie, Martin-Luther-Universitaet Halle-Wittenberg
🇩🇪Halle/Saale, Germany
Gemeinschaftspraxis, Onkologischer Schwerpunkt am Oskar-Helene-Heim
🇩🇪Berlin, Germany
BC Cancer Agency - Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Szent Margit Korhaz, Onkologia
🇭🇺Budapest, Hungary
CSSS Champlain-Charles-Le Moyne Local HS-0054
🇨🇦Greenfield Park, Quebec, Canada
Centre Paul Papin, CRLCC
🇫🇷ANGERS Cedex 9, France
CHD Vendee
🇫🇷La Roche Sur Yon, France
Martin-Luther-Universitaet Halle-Wittenberg
🇩🇪Halle/Saale, Germany
Frauenaerzte Pruener Gang Abts & Partner
🇩🇪Kiel, Germany
Klinik und Poliklinik fuer Frauenheilkunde und Geburtshilfe Universitaetsklinik Mainz
🇩🇪Mainz, Germany
Szabolcs-Szatmar-Bereg Megyei Korhazak es
🇭🇺Nyiregyhaza, Hungary
Mater Private Hospital
🇮🇪Dublin, Ireland
Petz Aladar Megyei Oktato Korhaz, Onkoradiologia
🇭🇺Gyor, Hungary
Mutterhaus der Borromaeerinnen, Innere Medizin I
🇩🇪Trier, Germany
Borsod-Abauj-Zemplen Megyei Korhaz és Egyetemi Oktato Korhaz, Onkologia
🇭🇺Miskolc, Hungary
Orszagos Onkologiai Intezet, Kemoterapia B
🇭🇺Budapest, Hungary
Bon Secours Hospital
🇮🇪Cork, Ireland
Federal State Budgetary Scientific Institution
🇷🇺Moscow, Russian Federation
Markusovszky Egyetemi Oktatokorhaz, Onkoradiologiai Osztaly
🇭🇺Szombathely, Hungary
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
State Budgetary Healthcare Institution "Samara Regional Clinical Oncology Dispensary"
🇷🇺Samara, Russian Federation
Republican Clinical Oncology Dispensary of the Ministry of Health of Bashkortostan Republic
🇷🇺Ufa, Russian Federation
Municipal clinical treatment-and-propyilactic institution "Donetsk regional oncology center',
🇺🇦Donetsk, Ukraine
Ospedale Villa San Pietro
🇮🇹Roma, Italy
St. James's Hospital
🇮🇪Dublin 8, Ireland
St. Vincent's University Hospital
🇮🇪Dublin, Ireland
M.O. di Oncologia - Azienda USL di Rimini - Ospedale "Cervesi"
🇮🇹Cattolica, Italy
Azienda Unita Sanitaria Locale di Rimini, U.O. di Oncologia ed Oncoematologia Ospedale degli Infermi
🇮🇹Rimini, Italy
Divisione Oncologia Medica Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST
🇮🇹Meldola, FC, Italy
Ospedale Civile di Faenza Centro Oncologico
🇮🇹Faenza, RA, Italy
Unita' Operativa di Oncologia, Ospedale Civile di Lugo
🇮🇹Lugo, RA, Italy
National Cancer Center, Center for Breast Cancer
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Ico-Hospitalet
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Department of Oncology and Medical Radiology, SI "DMA of MOH, Ukraine, "MI "Dnipropetrovsk City
🇺🇦Dnipropetrovsk, Ukraine
Kyiv City Clinical Oncologic Center
🇺🇦Kyiv, Ukraine
Pyatigorsk Oncology Center
🇷🇺Pyatigorsk, Russian Federation
Lviv State Oncologic Regional Treatment and Diagnostic Centre
🇺🇦Lviv, Ukraine