A Study of Pertuzumab in Addition to Chemotherapy and Trastuzumab as Adjuvant Therapy in Participants With Human Epidermal Growth Receptor 2 (HER2)-Positive Primary Breast Cancer (APHINITY)

• ClinicalTrials.gov Identifier: NCT01358877
• Recruitment Status: Active, not recruiting
• First Posted: May 24, 2011
• Results First Posted: January 5, 2018
• Last Update Posted: April 10, 2024
• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.; Breast International Group
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This randomized, double-blind, placebo-controlled, two-arm study will assess the safety and efficacy of pertuzumab in addition to chemotherapy plus trastuzumab as adjuvant therapy in participants with operable HER2-positive primary breast cancer. This study will be carried out in collaboration with the Breast International Group (BIG).

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: 5-Fluorouracil; Drug: Carboplatin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Placebo; Drug: Trastuzumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4804 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer
• Actual Study Start Date: November 8, 2011
• Actual Primary Completion Date: December 19, 2016
• Estimated Study Completion Date: November 28, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pertuzumab + Trastuzumab + Chemotherapy; Participants will receive pertuzumab (840 mg loading dose, then 420 mg) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) intravenously (IV) every 3 weeks (Q3W) for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 mg/m^2 + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 once weekly (QW); 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin area under the curve (AUC) 6 (up to 900 mg).	Drug: 5-Fluorouracil; 5-Fluorouracil will be administered as per the schedule specified in the respective arm.; Drug: Carboplatin; Carboplatin will be administered as per the schedule specified in the respective arm.; Drug: Cyclophosphamide; Cyclophosphamide will be administered as per the schedule specified in the respective arm.; Drug: Docetaxel; Docetaxel will be administered as per the schedule specified in the respective arm.; Drug: Doxorubicin; Doxorubicin will be administered as per the schedule specified in the respective arm.; Drug: Epirubicin; Epirubicin will be administered as per the schedule specified in the respective arm.; Drug: Paclitaxel; Paclitaxel will be administered as per the schedule specified in the respective arm.; Drug: Pertuzumab; Pertuzumab will be administered as per the schedule specified in the respective arm.; Other Name: Perjeta®; Drug: Trastuzumab; Trastuzumab will be administered as per the schedule specified in the respective arm.; Other Name: Herceptin®
Placebo Comparator: Placebo + Trastuzumab + Chemotherapy; Participants will receive placebo matching to pertuzumab IV Q3W and trastuzumab (8 milligrams per kilogram [mg/kg] loading dose, then 6 mg/kg) IV Q3W for 1 year (maximum 18 cycles) in combination with 1 of the following IV chemotherapy regimen (anthracycline-based or nonanthracycline-based) per Investigator's choice: 1) 3-4 cycles (Q3W) of 5-fluorouracil 500-600 milligrams per square meter (mg/m^2) + epirubicin 90-120 mg/m^2 or doxorubicin 50 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W (100 mg/m^2 for 3 cycles, 75 mg/m^2 in first cycle and 100 mg/m^2 in subsequent cycles, or 75 mg/m^2 for 4 cycles) or 12 cycles of paclitaxel 80 mg/m^2 QW; 2) 4 cycles (Q3W) of doxorubicin 60 mg/m^2 or epirubicin 90-120 mg/m^2 + cyclophosphamide 500-600 mg/m^2 followed by either 3-4 cycles of docetaxel Q3W or 12 cycles of paclitaxel QW (as described in Option 1); 3) 6 cycles (Q3W) of docetaxel 75 mg/m^2 + carboplatin AUC 6 (up to 900 milligrams [mg]).	Drug: 5-Fluorouracil; 5-Fluorouracil will be administered as per the schedule specified in the respective arm.; Drug: Carboplatin; Carboplatin will be administered as per the schedule specified in the respective arm.; Drug: Cyclophosphamide; Cyclophosphamide will be administered as per the schedule specified in the respective arm.; Drug: Docetaxel; Docetaxel will be administered as per the schedule specified in the respective arm.; Drug: Doxorubicin; Doxorubicin will be administered as per the schedule specified in the respective arm.; Drug: Epirubicin; Epirubicin will be administered as per the schedule specified in the respective arm.; Drug: Paclitaxel; Paclitaxel will be administered as per the schedule specified in the respective arm.; Drug: Placebo; Placebo will be administered as per the schedule specified in the respective arm.; Drug: Trastuzumab; Trastuzumab will be administered as per the schedule specified in the respective arm.; Other Name: Herceptin®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [i.e.], an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event.
2. Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: 3 years ]
   Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event.

Secondary Outcome Measures :

1. Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
2. Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: 3 years ]
   Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site).
3. Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants with DFS event is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
4. Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: 3 years ]
   Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS.
5. Percentage of Participants Who Died [ Time Frame: Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants who died due to any cause is reported.
6. Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3 [ Time Frame: 3 years ]
   The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years.
7. Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
8. Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: 3 years ]
   Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined as local, regional or distant breast cancer recurrence.
9. Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months) ]
   Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence.
10. Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings [ Time Frame: 3 years ]
    Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence.
11. Percentage of Participants With Primary Cardiac Event [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]
    Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.
12. Percentage of Participants With Secondary Cardiac Event [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]
    Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB).
13. Change From Baseline in LVEF to Worst Post-Baseline Value [ Time Frame: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months) ]
    LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
14. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score [ Time Frame: Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36 ]
    EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement.
15. Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning and positive values indicated improvement.
16. Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 disease/treatment-related symptom scores were linearly transformed on a scale of 0 to 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicated improvement in symptoms and positive values indicated worsening of symptoms.
17. Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties and positive values indicated worsening of financial difficulties.
18. Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
19. Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL.
20. Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding.
21. Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding.
22. Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding.
23. Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding.
24. Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain [ Time Frame: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36 ]
    EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding.
25. Trough Serum Concentration (Cmin) of Pertuzumab [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]
26. Cmin of Trastuzumab [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]
27. Peak Serum Concentration (Cmax) of Pertuzumab [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]
28. Cmax of Trastuzumab [ Time Frame: Cycles 1, 10 and 15 (Cycle length=21 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Non-metastatic operable primary invasive HER2-positive carcinoma of the breast that is histologically confirmed, and adequately excised
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (</=) 1
• Known hormone receptor status (estrogen receptor and progesterone receptor)
• The interval between definitive surgery for breast cancer and the first dose of chemotherapy must be no more than 8 weeks (56 days). The first cycle of chemotherapy must be administered within 7 days of randomization or on Day 56, whichever occurs first
• Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 55 percent (%) measured by echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
• Confirmed HER2 positive status
• Completion of all necessary baseline laboratory and radiologic investigations prior to randomization
• Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the participant and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug

Exclusion Criteria:

• History of any prior (ipsi- and/or contralateral) invasive breast cancer
• History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin
• Any "clinical" T4 tumor as defined by primary tumor/regional lymph nodes/distant metastasis (TNM), including inflammatory breast cancer
• Any node-negative tumor
• Any previous systemic chemotherapy for cancer or radiotherapy for cancer
• Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer
• Concurrent anti-cancer treatment in another investigational trial
• Serious cardiac or cardiovascular disease or condition
• Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness
• Abnormal laboratory tests immediately prior to randomization
• Pregnant or lactating women
• Sensitivity to any of the study medications or any of the ingredients or excipients of these medications

Contacts and Locations

Locations

United States, Arizona

HonorHealth Research Institute ? Bisgrove

Scottsdale, Arizona, United States, 85258

United States, California

Providence Regional Medical Center

Everett, California, United States, 98208

Marin Cancer Care Inc

Greenbrae, California, United States, 94904

Kaiser Permanente - Hayward

Hayward, California, United States, 94545

UCSD Moores Cancer Center

La Jolla, California, United States, 92093

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Kaiser Permanente - Oakland

Oakland, California, United States, 94611

Kaiser Permanente - Roseville

Roseville, California, United States, 95661

Sutter Cancer Center

Sacramento, California, United States, 95816

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States, 95825

Southern California Kaiser Permanente

San Diego, California, United States, 92108

K. Permanente - San Fransisco

San Francisco, California, United States, 94115

K. Permanente - San Jose

San Jose, California, United States, 95119

K. Permanente - Santa Clara

Santa Clara, California, United States, 95051

K. Permanente - S. San Fran

South San Francisco, California, United States, 94080

Kaiser Permanente; Oncology Clinical Trials

Vallejo, California, United States, 94589

K. Permanente - Walnut Creek

Walnut Creek, California, United States, 94596

United States, Colorado

Rocky Mountain Cancer Center - Denver

Littleton, Colorado, United States, 80120

Lutheran Hematology &Oncology

Wheat Ridge, Colorado, United States, 80033

United States, Connecticut

Eastern Ct Hema/Onco Assoc; Dept of Oncology

Norwich, Connecticut, United States, 06360

United States, District of Columbia

Washington Cancer Institute at MedStar Washington Hospital Center.

Washington, District of Columbia, United States, 20010

Georgetown U; Lombardi Comp Can

Washington, District of Columbia, United States, 20016-1468

United States, Florida

Florida Cancer Specialists; SCRI

Fort Myers, Florida, United States, 33901

Memorial Cancer Institute

Hollywood, Florida, United States, 33021

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States, 32224

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, United States, 32256

Ocala Oncology Center

Ocala, Florida, United States, 34471

Memorial Breast Cancer Center

Pembroke Pines, Florida, United States, 33028-1006

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States, 34952

Florida Cancer Specialists; Saint Petersburg

Saint Petersburg, Florida, United States, 33719

Florida Cancer Specialists, Research Department

West Palm Beach, Florida, United States, 33401

United States, Georgia

Phoebe Putney Memorial Hospital

Albany, Georgia, United States, 31701

Georgia Cancer Specialists

Atlanta, Georgia, United States, 30341

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, United States, 30060

United States, Idaho

Kootenai Cancer Center

Post Falls, Idaho, United States, 83854

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

Uni of Chicago

Chicago, Illinois, United States, 60637

Ingalls Memorial Hospital

Harvey, Illinois, United States, 60426

Loyola University Med Center

Maywood, Illinois, United States, 60153

Edward Cancer Center Naperville

Naperville, Illinois, United States, 60540

Illinois Cancer Care

Peoria, Illinois, United States, 61615

Edward Cancer Center Plainfield

Plainfield, Illinois, United States, 60585

Quincy Medical Group; Canc Ctr at Blessing Hosp

Quincy, Illinois, United States, 62301

Carle Foundation

Urbana, Illinois, United States, 61801

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

Cancer Center of Kansas

Wichita, Kansas, United States, 67214-3728

United States, Louisiana

Cancer Center of Acadiana at Lafayette General

Lafayette, Louisiana, United States, 70506

United States, Maine

Cancer Care of Maine

Brewer, Maine, United States, 04412

New England Cancer Specialists

Scarborough, Maine, United States, 04074

United States, Maryland

Mercy Medical Center

Baltimore, Maryland, United States, 21202

Weinberg CA Inst Franklin Sq

Baltimore, Maryland, United States, 21237

Maryland Oncology & Hematology, PA

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Massachusetts General Hospital.

Boston, Massachusetts, United States, 02114

Boston Medical Center

Boston, Massachusetts, United States, 02118

Dana Farber Cancer Institute at Faulkner Hospital

Boston, Massachusetts, United States, 02130

Beth Israel Deac Med Ctr; East Campus Rsch Pharmacy

Boston, Massachusetts, United States, 02215

Dana Farber Can Ins

Boston, Massachusetts, United States, 02215

Berkshire Hematology, Oncology Pc

Pittsfield, Massachusetts, United States, 01201

United States, Michigan

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States, 49503

West Michigan Cancer Center

Kalamazoo, Michigan, United States, 49007

United States, Minnesota

Southdale Cancer Clinic

Edina, Minnesota, United States, 55414

Coborn Cancer Center

Saint Cloud, Minnesota, United States, 56303

Metro-Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States, 55416

United States, Mississippi

Jackson Oncology Associates, PLLC

Jackson, Mississippi, United States, 39202

United States, Missouri

University of Missouri-Columbia; Ellis Fischel Cancer Center

Kansas City, Missouri, United States, 64108

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Heartland CCOP/Missouri Baptist Medical Center

Saint Louis, Missouri, United States, 63131

United States, Nebraska

Cancer Alliance of Nebraska

Lincoln, Nebraska, United States, 68510

Cancer Alliance of Nebraska

Omaha, Nebraska, United States, 68106

United States, New Hampshire

Dartmouth Hitchcock Med Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Saint Barnabas Medical Center

Livingston, New Jersey, United States, 07039

United States, New York

New York Oncology Hematology, P.C.

Albany, New York, United States, 12206

Montefiore Medical Center

Bronx, New York, United States, 10467

Roswell Park Cancer Inst.

Buffalo, New York, United States, 14263

Mount Sinai Beth Israel Medical Center

New York, New York, United States, 10003

Mount Sinai Beth Israel Comprehensive Cancer Center

New York, New York, United States, 10011

Mount Sinai West

New York, New York, United States, 10019

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United States, North Carolina

University of North Carolina-Chapel Hill

Chapel Hill, North Carolina, United States, 27599

Carolina Oncology Specialists, PA - Hickory

Hickory, North Carolina, United States, 28602

United States, Ohio

Dayton Clinical Oncology Prog

Centerville, Ohio, United States, 45459

Oncology Hematology Care Inc

Cincinnati, Ohio, United States, 45242

The Mark H. Zangmeister Ctr; Mid Ohio Onc/Hem Inc.

Columbus, Ohio, United States, 43219

Toledo Clinic Cancer Center

Toledo, Ohio, United States, 43623-3536

United States, Oregon

Northwest Cancer Specialists - Portland (NE Hoyt St)

Portland, Oregon, United States, 97213

United States, Pennsylvania

Abramson Cancer Center; Univ of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Albert Einstein Healthcare Network ; Cancer Center

Philadelphia, Pennsylvania, United States, 19141

Magee Womens Hospital

Pittsburgh, Pennsylvania, United States, 15213

United States, South Carolina

Charleston Oncology, P .A

Charleston, South Carolina, United States, 29414

Roper Bon Secours St. Francis Cancer Center

Charleston, South Carolina, United States, 29414

South Carolina Oncology Associates - SCRI

Columbia, South Carolina, United States, 29210

Cancer Centers of the Carolina; Eastside Medical Center

Greenville, South Carolina, United States, 29615

United States, South Dakota

Sanford USD School of Medicine

Sioux Falls, South Dakota, United States, 57104

United States, Tennessee

Tennessee Oncology , PLLC - Chattanooga

Chattanooga, Tennessee, United States, 37404

Tennessee Onc., PLLC - SCRI

Nashville, Tennessee, United States, 37203

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States, 37204

United States, Texas

Texas Oncology-Medical City Dallas

Dallas, Texas, United States, 75230

Texas Oncology - DFW at Dallas Presbyterian Hospital

Dallas, Texas, United States, 75231

Texas Oncology - DFW

Dallas, Texas, United States, 75246

Texas Oncology-El Paso Cancer Treatment Center Grandview

El Paso, Texas, United States, 79902

Texas Oncology - DFW Fort Worth

Fort Worth, Texas, United States, 76104

The Center for Cancer and Blood Disorders - Fort Worth

Fort Worth, Texas, United States, 76104

Texas Oncology, P.A. - Garland

Garland, Texas, United States, 77060

Texas Oncology - Houston (Gessner)

Houston, Texas, United States, 77024

Texas Oncology-Tyler

Irving, Texas, United States, 75063

Cancer Care Centers of South Texas-HOAST - San Antonio

New Braunfels, Texas, United States, 78130

Texas Oncology - DFW Plano

Plano, Texas, United States, 75075

United States, Utah

Community Cancer Trials of Utah

Ogden, Utah, United States, 84405

United States, Virginia

Wellmonth Physician Services

Bristol, Virginia, United States, 24201

Virginia Cancer Institute

Richmond, Virginia, United States, 23229

United States, Washington

Providence St. Mary Regional Cancer Center

Walla Walla, Washington, United States, 99362

United States, West Virginia

West Virginia University Hospitals Inc

Morgantown, West Virginia, United States, 26056

United States, Wisconsin

Green Bay Oncology/St. Mary?s Hospital

Green Bay, Wisconsin, United States, 54301

Marshfield Clinic

Marshfield, Wisconsin, United States, 54449

Argentina

Centro Medico San Roque

San Miguel de Tucuman, Argentina, T4000IAK

Isis Centro Especializado de Luces; Oncology

Santa Fe, Argentina, S3000XAE

Australia, New South Wales

Lismore Base Hospital; Cancer Care & Haematology Unit

Lismore, New South Wales, Australia, 2480

Mater Misericordiae Hospital; Chemotherapy Cottage

Sydney, New South Wales, Australia, 2060

Newcastle Mater Misericordiae Hospital; Oncology

Waratah, New South Wales, Australia, 2298

Westmead Hospital; Medical Oncology and Pallative Care

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Wesley Medical Centre; Clinic For Haematology and Oncology

Auchenflower, Queensland, Australia, 4066

Mater Hospital; Oncology

Brisbane, Queensland, Australia, 4101

Australia, South Australia

Royal Adelaide Hospital; Oncology

Adelaide, South Australia, Australia, 5000

Australia, Tasmania

Royal Hobart Hospital; Medical Oncology

Hobart, Tasmania, Australia, 7000

Australia, Victoria

Monash Medical Centre; Oncology

Clayton, Victoria, Australia, 3168

Geelong Hospital; Andrew Love Cancer Centre

Geelong, Victoria, Australia, 3220

Austin Hospital; Medical Oncology

Heidelberg, Victoria, Australia, 3084

Peter Maccallum Cancer Institute; Medical Oncology

Melbourne, Victoria, Australia, 3000

Australia, Western Australia

Sir Charles Gairdner Hospital; Medical Oncology

Perth, Western Australia, Australia, 6009

Austria

Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I

Graz, Austria, 8036

Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

Innsbruck, Austria, 6020

Ordensklinikum Linz Barmherzige Schwestern; Abt. fur Innere Medizin 1

Linz, Austria, 4010

Lhk Feldkirch; Interne Medizin Abt.

Rankweil, Austria, 6830

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

Salzburg, Austria, 5020

A. Ö. Krankenhaus Der Barmherzigen Brüder; Interne Abt.

St Veit An Der Glan, Austria, 9300

Lkh Vöcklabruck; I. Abt. Für Innere Medizin

Vöcklabruck, Austria, 4840

Klinikum Kreuzschwestern Wels; Iii. Interne Abt.

Wels, Austria, 4600

Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie

Wien, Austria, 1090

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie

Wien, Austria, 1090

Krankenhaus Der Stadt Wien-Hietzing; Abt. Für Gynäkologie U. Geburtshilfe

Wien, Austria, 1130

Belgium

Institut Jules Bordet

Anderlecht, Belgium, 1070

GHdC Site Notre Dame

Charleroi, Belgium, 6000

UZ Antwerpen

Edegem, Belgium, 2650

Jessa Zkh (Campus Virga Jesse)

Hasselt, Belgium, 3500

AZ Groeninge

Kortrijk, Belgium, 8500

UZ Leuven Gasthuisberg

Leuven, Belgium, 3000

CHU Sart-Tilman

Liège, Belgium, 4000

Clinique Ste-Elisabeth

Namur, Belgium, 5000

Sint Augustinus Wilrijk

Wilrijk, Belgium, 2610

Bulgaria

UMHAT Tsaritsa Yoanna - ISUL; Clinic of Oncotherapy

Sofia, Bulgaria, 1527

SHATO - Sofia

Sofia, Bulgaria, 1756

SHATOD Dr. Marko Antonov Markov-Varna, EOOD

Varna, Bulgaria, 9010

Canada, Alberta

Tom Baker Cancer Centre; Dept of Medicine

Calgary, Alberta, Canada, T2N 4N2

Cross Can Inst

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

BC Cancer Agency, CSI

Kelowna, British Columbia, Canada, V1Y 5L3

BC Cancer ? Surrey

Surrey, British Columbia, Canada, V3V 1Z2

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

Bcca - Vancouver Island Cancer Centre; Oncology

Victoria, British Columbia, Canada, V8R 6V5

Canada, Manitoba

CancerCare Manitoba; Neuro-Oncology

Winnipeg, Manitoba, Canada, R2H 2A6

Canada, New Brunswick

Atlantic Health Science Corporation; Saint John Regional Hospital Facility

Saint John, New Brunswick, Canada, E2L 4L2

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

Cancer Centre of Southeastern Ontario; Kingston General Hospital

Kingston, Ontario, Canada, K7L 5P9

London Health Sciences Centre

London, Ontario, Canada, N6A 4L6

Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre

Mississauga, Ontario, Canada, L5M 2N1

Southlake Regional Health Center

Newmarket, Ontario, Canada, L3Y 2R2

Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada, K1H 1C4

Niagara Health Systems - St. Catherines General Site; Niagara Health System-St. Catharines Site

St. Catharines, Ontario, Canada, L2R 7C6

Northeastern Ontario; Regional Cancer Centre

Sudbury, Ontario, Canada, P3E 5J1

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada, M4N 3M5

Mount Sinai Hospital

Toronto, Ontario, Canada, M5G 1X5

Princess Margaret Cancer Center

Toronto, Ontario, Canada, M5G 1Z5

Canada, Quebec

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, Canada, H1T 2M4

Chum Hopital Notre Dame; Centre D'Oncologie

Montreal, Quebec, Canada, H2L 4M1

Hopital Sacre-Coeur Research Centre

Montreal, Quebec, Canada, H4J 1C5

Hopital du Saint Sacrement

Quebec City, Quebec, Canada, G1S 4L8

Canada, Saskatchewan

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada, S4T 7T1

Chile

INTOP

Providencia, Chile, 7501089

Fundacion Arturo Lopez Perez

Santiago, Chile, 7500921

China

Cancer Hospital Chinese Academy of Medical Sciences.

Beijing, China, 100021

The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)

Beijing, China, 100071

the First Hospital of Jilin University

Changchun, China, 130021

Jilin Cancer Hospital

Changchun, China, 132013

Hu Nan Provincial Cancer Hospital

Changsha, China, 410006

Sichuan Provincial People's Hospital

Chengdu, China, 610072

Fujian Medical University Union Hospital

Fuzhou City, China, 350001

The 900th Hospital of PLA joint service support force

Fuzhou, China, 110016

Sun Yet-sen University Cancer Center

Guangzhou City, China, 510663

Guangdong General Hospital

Guangzhou, China, 510080

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, China, 310003

Harbin Medical University Cancer Hospital

Harbin, China, 150081

The 1st Affiliated Hospital of Nanchang Unversity

Nanchang, China, 330019

Fudan University Shanghai Cancer Center

Shanghai City, China, 200120

Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)

Shanghai, China, 200025

Shanghai First People's Hospital

Shanghai, China, 200080

Changhai Hospital of Shanghai

Shanghai, China, 200433

Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)

Shijiazhuang, China, 050035

Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology

Wuhan, China, 430022

Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech

Wuhan, China, 430030

Hubei Cancer Hospital

Wuhan, China, 430079

Colombia

Inst. Nacional de Cancerologia; Clinica de Seno

Bogota, Colombia, 111511

Fundacion Cardioinfantil

Bogota, Colombia

Hospital Pablo Tobon Uribe

Medellin, Colombia, 050034

Oncomedica S.A.

Monteria, Colombia, 230002

Croatia

Uni Hospital Split; Oncology & Radiotherapy

Split, Croatia, 21000

General Hospital Varazdin

Varazdin, Croatia, 42000

Clinical Hospital Centre Zagreb

Zagreb, Croatia, 10000

Czechia

Masarykuv onkologicky ustav

Brno, Czechia, 656 53

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

Hradec Kralove, Czechia, 500 05

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, Czechia, 779 00

MULTISCAN, s.r.o., Radiologicke centrum Pardubice

Pardubice, Czechia, 532 03

Denmark

Aalborg Universitetshospital; Onkologisk Afdeling

Aalborg, Denmark, 9000

Sydvestjysk Sygehus Esbjerg; Onkologisk afdeling

Esbjerg, Denmark, 6700

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, Denmark, 2730

Nordsjællands Hospital, Hillerød, Onkologisk Afdeling

Hillerod, Denmark, 3400

Rigshospitalet; Onkologisk Klinik

København Ø, Denmark, 2100

Sjællands Universitetshospital, Næstved; Onkologisk Afdeling

Naestved, Denmark, 4700

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, Denmark, 5000

Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium

Roskilde, Denmark, 4000

Vejle Sygehus; Onkologisk Afdeling

Vejle, Denmark, 7100

El Salvador

Hospital Oncologia; Oncology

Salvador, El Salvador, 01101

Hospital Diagnostico Escalón

San Salvador, El Salvador, 01101

France

Clinique De L Europe; Pmsi

Amiens, France, 80090

ICO Paul Papin; Oncologie Medicale.

Angers, France, 49055

HOP Prive Arras Les Bonnettes; Chimiotherapie

Arras, France, 62012

Institut Sainte Catherine

Avignon, France, 84082

ICONE

Bezannes, France, 51430

Institut Bergonie; Oncologie

Bordeaux, France, 33076

Polyclinique Bordeaux Nord

Bordeaux, France, 33300

Hopital Augustin Morvan; Federation De Cancerologie

Brest, France, 29200

Centre Francois Baclesse; Recherche Clinique

Caen, France, 14076

Centre Jean Perrin; Hopital De Jour

Clermont Ferrand, France, 63011

Centre Leonard De Vinci;Chimiotherapie

Dechy, France, 59187

Centre Georges-François Lecler; Ctr de Lutte Contre le Canc

Dijon, France, 21034

Institut Daniel Hollard

Grenoble, France, 38000

Centre Hospitalier Departemental Les Oudairies

La Roche Sur Yon, France, 85925

Clinique des Ormeaux; Oncologie

Le Havre, France, 76600

Centre Oscar Lambret; Cancerologie Gynecologique

Lille, France, 59020

Hopital Dupuytren; Oncologie Medicale

Limoges, France, 87042

Centre Leon Berard; Departement Oncologie Medicale

Lyon, France, 69373

Institut Paoli Calmettes; Oncologie Medicale

Marseille, France, 13273

Institut régional du Cancer Montpellier

Montpellier, France, 34298

Polyclinique De Gentilly; Hemodialyse

Nancy, France, 54100

Centre Antoine Lacassagne; Hopital De Jour A2

Nice, France, 06189

Institut de cancerologie du Gard

Nimes, France, 30029

Institut Curie; Oncologie Medicale

Paris, France, 75231

Ch Pitie Salpetriere; Cmrr Ile De France Salpetriere

Paris, France, 75651

Polyclinique Francheville; MED CHIMIOTHERAPIE RADIOTHERAPIE

Perigueux, France, 24000

Clinique Armoricaine Radiologie; Hopital de Jour

Plerin, France, 22190

Chu De Poitiers; Chu La Miletrie

Poitiers, France, 86021

Institut Jean Godinot; Hopital De Jour

Reims, France, 51056

Centre Eugene Marquis; Unite Huguenin

Rennes, France, 35042

Centre Henri Becquerel; Oncologie Medicale

Rouen, France, 76038

Ico Rene Gauducheau; Oncologie

Saint Herblain, France, 44805

ICL; Hematologie

Saint-Priest en Jarez, France, 42271

Centre Rene Huguenin; CONSULT SPECIALISEES

St Cloud, France, 92210

Institut d'oncologie de l'Orangerie; Chimiotherapie

Strasbourg, France, 67010

Hopital Hautepierre; Hematologie Oncologie

Strasbourg, France, 67098

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, France, 31059

Clinique Pasteur; Pneumologie

Toulouse, France, 31076

Centre Alexis Vautrin; Oncologie Medicale

Vandoeuvre-les-nancy, France, 54519

Institut Gustave Roussy; Oncologie Medicale

Villejuif, France, 94800

Germany

Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie

Amberg, Germany, 92224

Hochwaldkrankenhaus

Bad Nauheim, Germany, 61231

Evang. Krankenhaus Frauenklinik

Bergisch Gladbach, Germany, 51465

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)

Berlin, Germany, 10367

Praxis Dr. Schoenegg

Berlin, Germany, 10719

HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe

Berlin, Germany, 13125

Frauenarzt-Zentrum Zehlendorf an der Teltower Eiche

Berlin, Germany, 14169

Onkologische Schwerpunktpraxis Bielefeld; Haemotologie & Internistische onkologie

Bielefeld, Germany, 33604

Universitätsklinikum Bonn; Zentrum für Geburtshilfe und Frauenheilkunde

Bonn, Germany, 53127

Praxis Dr. Ralf Lorenz

Braunschweig, Germany, 38100

Hämato-Onkologie im Medicum/Home

Bremen, Germany, 28209

Klinikum Sindelfingen-Böblingen; Frauenklinik

Böblingen, Germany, 71032

Klinikum Chemnitz gGmbH; Frauen- und Kinderklinik

Chemnitz, Germany, 09116

DONAU ISAR Klinikum Deggendorf; Frauenklinik

Deggendorf, Germany, 94469

St. Johannes-Hospital

Dortmund, Germany, 44137

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf; Frauenklinik

Düsseldorf, Germany, 40225

Luisenkrankenhaus GmbH & Co. KG., Brustzentrum

Düsseldorf, Germany, 40235

Praxis für Hamatologie und Onkologie

Erfurt, Germany, 99085

Universitätsklinikum Erlangen; Frauenklinik

Erlangen, Germany, 91054

Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe

Esslingen, Germany, 73730

Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus

Frankfurt am Main, Germany, 60389

Klinik Johann Wolfgang von Goethe Uni; Klinik für Frauenheilkunde und Geburtshilfe

Frankfurt, Germany, 60596

Städtische Kliniken Frankfurt am Main Höchst

Frankfurt, Germany, 65929

Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

Freiburg, Germany, 79110

Dres.Jochen Wilke und Harald Wagner

Fürth, Germany, 90766

Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum

Greifswald, Germany, 17475

Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie

Halle, Germany, 06120

Universitätsklinikum Hamburg-Eppendorf; Frauenklinik

Hamburg, Germany, 20246

SANA Klinikum Hameln-Pyrmont; Frauenklinik / Brustzentrum

Hameln, Germany, 31785

MVZ Onko Medical GmbH Hannover, Ralf Lohse (Geschäftsführer)

Hannover, Germany, 30177

Diakovere Henriettenstift, Frauenklinik

Hannover, Germany, 30559

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, Germany, 69120

Praxisgemeinschaft; Frauenärzte am Bahnhofsplatz

Hildesheim, Germany, 31134

Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe

Homburg/Saar, Germany, 66424

ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG; Frauenklinik

Karlsruhe, Germany, 76135

Elisabeth-Krankenhaus Brustzentrum

Kassel, Germany, 34117

Klinikum Kassel GmbH; Klinik für Frauenheilkunde und Geburtshilfe

Kassel, Germany, 34125

UNI-Klinikum Campus Kiel Klinik für Gynäkologie und Geburtshilfe

Kiel, Germany, 24105

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

Koeln, Germany, 50935

Uniklinik Köln, Klinik und Poliklinik und Geburtshilfe; Brustzentrum Köln

Köln, Germany, 50931

Klinikum Landshut Frauenklinik

Landshut, Germany, 84034

Sankt Elisabeth Krankenhaus; Gynaekology

Leipzig, Germany, 04277

Evangelisches Krankenhaus; Abt. Gynäkologie und Geburtshilfe

Ludwigsfelde, Germany, 14974

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Frauenheilkunde und Geburtshilfe

Lübeck, Germany, 23538

Universitätsmedizin Mainz; Klinik u. Poliklinik f. Geburtshilfe u. Frauenheilkunde

Mainz, Germany, 55131

Rotkreuzklinikum München; Frauenklinik

Muenchen, Germany, 80637

Brustzentrum Rhein-Ruhr Servicegesellschaft mbH

Mönchengladbach, Germany, 41061

Klinikum der Universität München; Frauenklinik - Onkologie II

München, Germany, 80336

Klinikum rechts der Isar der TU München; Klinik und Poliklinik für Frauenheilkunde

München, Germany, 81675

Universitätsklinikum Münster; Klinik für Frauenheilkunde und Geburtshilfe

Münster, Germany, 48149

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, Germany, 63069

Medizinisches Versorgungszentrum am Klinikum Oldenburg GmbH

Oldenburg, Germany, 26133

Hämatologisch/Onkologische Praxis Prof. Dr. Decker, Studienzentrum

Ravensburg, Germany, 88212

Oncologianova GmbH

Recklinghausen, Germany, 45659

RoMed Klinikum Rosenheim; Klinik für Gynäkologie und Geburtshilfe

Rosenheim, Germany, 83022

Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

Rostock, Germany, 18059

MVZ für Hämatologie, Onkologie, Strahlentherapie und Palliativmedizin -; Klinik Dr. Hancken

Stade, Germany, 21680

Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie

Trier, Germany, 54290

Universitätsklinik Tübingen; Frauenklinik

Tübingen, Germany, 72076

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

Ulm, Germany, 89075

Dres. Arnd Nusch Naser Ali-Mohammad Kalhori und Werner Langer

Velbert, Germany, 42551

Schwarzwald-Baar Klinikum Klinik für Frauenheilkunde und Geburtshilfe

Villingen-Schwenningen, Germany, 78052

St. Josefs-Hospital Wiesbaden

Wiesbaden, Germany, 65189

Marien-Hospital Witten; Frauenklinik Brustzentrum

Witten, Germany, 58452

Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker

Würzburg, Germany, 97080

Guatemala

Grupo Angeles

Guatemala City, Guatemala, 01015

Centro Oncológico Sixtino / Centro Oncológico SA

Guatemala, Guatemala, 01010

Hong Kong

Queen Mary Hospital; Surgery

Hong Kong, Hong Kong, 852

Queen Mary Hospital; Dept of Medicine

Hong Kong, Hong Kong

Hungary

Semmelweis Egyetem Onkologiai Központ

Budapest, Hungary, 1083

Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly

Budapest, Hungary, 1122

Magyar Honvedseg Egeszsegugyi Kozpont; Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Budapest, Hungary, H-1077

Debreceni Egyetem, Klinikai Kozpont, Onkologiai Klinika

Debrecen, Hungary, 4032

Petz Aladar Megyei Oktato Korhaz; Oncoradiologia

Gyor, Hungary, 9024

Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek

Gyula, Hungary, 5703

Bács-Kiskun Vármegyei Oktatókórház

Kecskemet, Hungary, 6000

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

Szeged, Hungary, 6720

Veszprem Megyei Csolnoky; Ferenc Korhaz

Veszprem, Hungary, 8200

Ireland

Cork Uni Hospital; Oncology Dept

Cork, Ireland

Mater Misericordiae Uni Hospital; Oncology

Dublin, Ireland, 7

Beaumont Hospital; Cancer Clinical Trials Unit

Dublin, Ireland, 9

St Vincent'S Uni Hospital; Medical Oncology

Dublin, Ireland, D04 T6F4

St. James Hospital; Oncology

Dublin, Ireland, D08 HNY1

Galway University Hospital; Clinical Trials Department

Galway, Ireland, H91YR71

University Hospital Limerick - Oncology

Limerick, Ireland

Israel

Rambam Medical Center; Oncology

Haifa, Israel, 3109601

Rabin MC; Davidof Center - Oncology Institute

Petach Tikva, Israel, 4941492

Chaim Sheba Medical Center; Oncology Dept

Ramat Gan, Israel, 5262100

Kaplan Medical Center; Oncology Inst.

Rehovot, Israel, 7610001

Sourasky / Ichilov Hospital; Oncology Department

Tel Aviv, Israel, 64239-06

Italy

Campus Universitario S.Venuta; Centro Oncologico T.Campanella

Catanzaro, Calabria, Italy, 88100

AORN'S.G.Moscati; Oncologia

Avellino, Campania, Italy, 83100

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

Napoli, Campania, Italy, 80131

Ist. Uni Federico Ii; Divisione Di Oncologia Medica - Dpt. Di Medicina Interna

Napoli, Campania, Italy, 80131

Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica

Bologna, Emilia-Romagna, Italy, 40138

Ospedale Ramazzini

Carpi, Emilia-Romagna, Italy, 41012

Arcispedale Santa Maria Nuova; Oncologia

Reggio Emilia, Emilia-Romagna, Italy, 42100

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica

Aviano, Friuli-Venezia Giulia, Italy, 33081

Divisione Onc Med dell'Azienda

Udine, Friuli-Venezia Giulia, Italy, 33100

Ospedale Belcolle Di Viterbo; Oncologia

Viterbo, Lazio, Italy, 01100

Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica

Genova, Liguria, Italy, 16128

Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical

Genova, Liguria, Italy, 16132

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genova, Liguria, Italy, 16132

ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica

Brescia, Lombardia, Italy, 25123

ASST DI LECCO; Oncologia Medica

Lecco, Lombardia, Italy, 23900

Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica

Milano, Lombardia, Italy, 20141

Policlinico di Monza; Istituto di Oncologia

Monza, Lombardia, Italy, 20052

IRCCS Fondazione Maugeri; Oncologia Medica I

Pavia, Lombardia, Italy, 27100

IRCCS Istituto Clinico Humanitas; Oncologia

Rozzano (MI), Lombardia, Italy, 20089

Az. Osp. Di Busto P.O. Di Saronno; U.O. Di Oncologia Medica

Saronno, Lombardia, Italy, 21047

Ospedale S. Croce Di Fano; Servizio Oncologia

Fano, Marche, Italy, 61032

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico

Candiolo, Piemonte, Italy, 10060

Ospedale Antonio Perrino; Oncologia Medica

Brindisi, Puglia, Italy, 72100

Nuovo Ospedale di Prato S. Stefano - Azienda USL Toscana Centro

Prato, Toscana, Italy, 59100

Ospedale Di Bolzano; Dept. Di Oncologia

Bolzano, Trentino-Alto Adige, Italy, 39100

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Perugia, Umbria, Italy, 06156

Azienda Ospedaliera S. Maria - Terni; Oncologia

Terni, Umbria, Italy, 05100

Ospedale Mater Salutis; Dept of Oncology

Legnago, Veneto, Italy, 37045

Japan

Aichi Cancer Center Hospital, Breast Oncology

Aichi, Japan, 464-8681

Chiba Cancer Center; Breast Surgical Oncology

Chiba, Japan, 260-8717

National Cancer Center Hospital East

Chiba, Japan, 277-8577

Natl Hosp Org Shikoku; Cancer Ctr, Surgery

Ehime, Japan, 791-0280

National Hospital Organization Kyushu Cancer Center;Breast Oncology

Fukuoka, Japan, 811-1395

Gunma University Hospital; Department of Thoracic and Visceral Organ Surgery

Gunma, Japan, 371-8511

Hiroshima City Hiroshima Citizens Hospital; Breast Surgery

Hiroshima, Japan, 730-8518

Iwate Med Univ School of Med; Surgery

Iwate, Japan, 028-3695

Sagara Hospital; Breast Surgery

Kagoshima, Japan, 892-0833

St. Marianna University School of Medicine Hospital, Breast and Endocrine Surgery

Kanagawa, Japan, 216-8511

Tokai University Hospital, Breast Surgery

Kanagawa, Japan, 259-1193

Kumamoto City Hospital, Breast and Endocrine Surgery

Kumamoto, Japan, 862-8505

Kumamoto Shinto General Hospital; Breast Cancer Center

Kumamoto, Japan, 862-8655

Kyoto University Hospital; Breast Surgery

Kyoto, Japan, 606-8507

Niigata Cancer Ctr Hospital; Breast Surgery

Niigata, Japan, 951-8566

National Hospital Organization Osaka National Hospital; Breast Surgery

Osaka, Japan, 540-0006

Osaka International Cancer Institute; Breast and Endocrine Surgery

Osaka, Japan, 541-8567

Saitama Medical University International Medical Center; Breast Oncology

Saitama, Japan, 350-1298

Saitama Cancer Center, Breast Oncology

Saitama, Japan, 362-0806

Shizuoka Cancer Center; Breast Surgery

Shizuoka, Japan, 411-8777

Shizuoka General Hospital; Breast Surgery

Shizuoka, Japan, 420-8527

Jichi Medical School ; Surgery

Tochigi, Japan, 329-0498

National Cancer Center Hospital; Medical Oncology

Tokyo, Japan, 104-0045

Tokyo Metropolitan; Komagome Hospital, Surgery

Tokyo, Japan, 113-8677

The Cancer Inst. Hosp. of JFCR; Breast Oncology Center

Tokyo, Japan, 135-8550

Tokyo Medical Uni. Hospital; Breast Oncology

Tokyo, Japan, 160-0023

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 463-707

Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology

Seoul, Korea, Republic of, 03080

Yonsei University Severance Hospital; Medical Oncology

Seoul, Korea, Republic of, 120-752

Kyunghee University Hospital; Endocrinology

Seoul, Korea, Republic of, 130-702

Samsung Medical Centre; Division of Hematology/Oncology

Seoul, Korea, Republic of, 135-710

Korea University Anam Hospital; Oncology Haemotology

Seoul, Korea, Republic of, 136-705

Mexico

Centro Estatal de Oncología de Campeche

Campehe, Campeche, Mexico, 24096

Fundacion Rodolfo Padilla Padilla A.C.

León, Guanajuato, Mexico, 37000

Núcleo de Especialidades Oncológicas

Guadalajara, Jalisco, Mexico, 44670

Hospital Angeles Metropolitano; Room 220

Mexico City, Mexico CITY (federal District), Mexico, 06760

Hospital General de México; Unidad de Oncologia

Mexico DF, Mexico CITY (federal District), Mexico, 06726

Centro Universitario Contra El Cancer

Monterrey, Nuevo LEON, Mexico, 64020

Centro de Diagnóstico y Tratamiento Integral de Mama, Hospital San José Tec de Monterrey

Montrrey, Nuevo LEON, Mexico, 64710

Oaxaca Site Management Organization

Oaxaca de Juárez, Oaxaca, Mexico, 68000

Cancerologia de Queretaro; Oncologia

Queretaro, Queretaro, Queretaro, Mexico, 76090

Médicos Especialistas en Cáncer SC

Aguascalientes, Mexico, 20230

Centro Estatal De Cancerologia De Durango; Oncology

Durango, Mexico, 34000

Centro Regional de Enfermedades Oncológicas, S.A.

San Luis Potosi, Mexico, 78218

Netherlands

Medisch Centrum Alkmaar

Alkmaar, Netherlands, 1815 JD

Amphia ziekenhuis, locatie langendijk

Breda, Netherlands, 4818 CK

Reinier de Graaf Gasthuis

Delft, Netherlands, 2625 AD

Academish Ziekenhuis Maastricht (Azm); Inwendige Geneeskunde

Maastricht, Netherlands, 6229 HX

Isala Klinieken

Zwolle, Netherlands, 8011 JW

New Zealand

Waikato Hospital; Dept of Medical Oncology

Hamilton, New Zealand, 3240

Palmerston North Hospital; Regional Cancer Treatment Service

Palmerston North, New Zealand, 4442

Panama

The Panama Clinic

Panama, Panama, 0832-02723

Centro Oncologico America

Panama, Panama, 0834-02723

Peru

Clinica Anglo Americana - Centro de Investigacion Oncologia CAA

Lima, Peru, L27

Instituto Nacional de Enfermedades Neoplasicas

Lima, Peru, Lima 34

Clinica El Golf

San Isidro, Peru, L27 Lima

Clinica Peruana Americana

Trujillo, Peru, 13011

Philippines

University Of Santo Tomas; Oncology; Benavides Cancer Institute

Manila, Philippines, 1008

Rizal Medical Center

Pasig City, Philippines, 1605

Veterans Memorial Medical Ctr; Cancer Research Centre

Quezon City, Philippines, 1101

Poland

Bialostockie Ctr Onkologii; Oddzial Chemioterapii Dziennej

Bialystok, Poland, 15-027

Centrum Onkologii;Im. Franciszka Lukaszczyka;Onkologii

Bydgoszcz, Poland, 85-796

Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii

Gdansk, Poland, 80-214

Opolskie Centrum Onkologii;Oddzial Onkologii Klinicznej

Opole, Poland, 45-061

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr

Warszawa, Poland, 02-781

NZOZ Mazowiecki Szpital Onkologiczny Uczelni Warszawskiej im. M. Sk?odowskiej-Curie

Wieliszew, Poland, 05-135

Romania

Emergency University Bucharest Hospital; Oncology Department

Bucharest, Romania, 050098

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj Napoca, Romania, 400015

Oncology Inst. Cluj-Napoca; Cancer Dept

Cluj-Napoca, Romania, 400015

Euroclinic Center of Oncology SRL

Iasi, Romania, 700106

Russian Federation

S.I. Russian Oncological Research Center n.a. N.N. Blokhin

Moscow, Moskovskaja Oblast, Russian Federation, 115478

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

Pyatigorsk, Stavropol, Russian Federation, 357502

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan, Tatarstan, Russian Federation, 420029

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

Samara, Russian Federation, 443031

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

Stavropol, Russian Federation, 355045

Tula Regional Oncology Dispensary

Tula, Russian Federation, 300053

Slovenia

Institute of Oncology Ljubljana

Ljubljana, Slovenia, 1000

South Africa

National Hospital; Oncotherapy Dept

Bloemfontein, South Africa, 9301

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

Johannesburg, South Africa, 2193

Steve Biko Academic Hospital; Oncology

Pretoria, South Africa, 0002

Spain

Hospital General Universitario de Elche; Servicio de Oncologia

Elche, Alicante, Spain, 03203

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, Spain, 08916

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain, 8208

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de La Barca, Barcelona, Spain, 08740

Hospital Universitario Marques de Valdecilla; Servicio de Oncologia

Santander, Cantabria, Spain, 39008

Hospital Provincial de Castellon; Servicio de Oncologia

Castellon de La Plana, Castellon, Spain, 12002

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain, 14004

IInstituto Oncologico de San Sebastian, Oncologikoa; Servicio de Oncologia

San Sebastian, Guipuzcoa, Spain, 20014

Hospital de Donostia; Servicio de Oncologia Medica

San Sebastian, Guipuzcoa, Spain, 20080

Hospital Universitario Son Espases

Palma De Mallorca, Islas Baleares, Spain, 07014

Hospital Son Llatzer; Servicio de Oncologia

Palma de Mallorca, Islas Baleares, Spain, 07198

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, Spain, 15706

Hospital Universitario de Canarias;servicio de Oncologia

La Laguna, Tenerife, Spain, 38320

Hospital del Mar; Servicio de Oncologia

Barcelona, Spain, 08003

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Spain, 08036

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, Spain, 08041

Hospital Duran i Reynals; Oncologia

Barcelona, Spain, 08907

Hospital Juan Ramon Jimenez;Servicio de Oncologia

Huelva, Spain, 21005

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

Jaen, Spain, 23007

Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

La Coruña, Spain, 15006

Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia

La Coruña, Spain, 15009

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lerida, Spain, 25198

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Spain, 28007

Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

Madrid, Spain, 28033

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, Spain, 28034

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Spain, 28041

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, Spain, 28050

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Malaga, Spain, 29010

Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia

Murcia, Spain, 30008

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

Salamanca, Spain, 37007

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Sevilla, Spain, 41009

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Sevilla, Spain, 41013

Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia

Sevilla, Spain, 41014

Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia

Toledo, Spain, 45004

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, Spain, 46009

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, Spain, 46010

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, Spain, 46015

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, Spain, 46026

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, Spain, 50009

Sweden

Sahlgrenska Universitetssjukhuset; Onkology

Gothenburg, Sweden, 41 343

Uni Hospital Linkoeping; Dept. of Oncology

Linköping, Sweden, 58185

Karolinska University Hospital; Department of General Oncology

Stockholm, Sweden, 11883

Norrlands Universitetssjukhus, Umeå, Cancercentrum; Dept of Oncology

Umea, Sweden, 90185

Akademiska sjukhuset, Onkologkliniken

Uppsala, Sweden, 751 85

Switzerland

Universitaetsspital Basel; Onkologie

Basel, Switzerland, 4031

Hôpitaux Universit. de Genève Gynécologique - Oncologie; Gynécologie

Genève 14, Switzerland, 1211

Luzerner Kantonsspital; Medizinische Onkologie

Luzern, Switzerland, 6004

Kantonsspital St. Gallen; Onkologie/Hämatologie

St. Gallen, Switzerland, 9007

Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich

Zürich, Switzerland, 8008

Taiwan

Changhua Christian Hospital; Dept of Surgery

Changhua, Taiwan, 500

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung, Taiwan, 807

Taichung Veterans General Hospital; Dept of Surgery

Taichung, Taiwan, 407

National Cheng Kung Uni Hospital; Surgery

Tainan, Taiwan, 704

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, Taiwan, 00112

National Taiwan Uni Hospital; General Surgery

Taipei, Taiwan, 100

Tri-Service General Hospital, Division of General Surgery

Taipei, Taiwan, 114

Thailand

Chiang Rai Prachanukraw Hospital; Department of Pediatrics, Faculty of Medicine

Chiang Rai, Thailand, 57000

Lopburi Cancer Hospital; Chemotherpy Unit; Chemotherapy

Lopburi, Thailand, 15000

Buddhachinaraj Phitsanulok Hospital; Chemotherapy Unit ; Department of Medicine

Phitsanuok, Thailand, 65000

Songklanagarind Hospital; Department of Surgery

Songkla, Thailand, 90110

Surat Thani Hospital

Surat Thani, Thailand, 84000

Ukraine

Cherkassy Regional Oncological Hospital

Cherkassy, Ukraine, 18009

State Medical Academy; Oncology

Dnipropetrovsk, Ukraine, 43102

Ivano-Frankivsk Regional Oncology Center

Ivano-Frankivsk, Ukraine, 76018

Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients

Kiev, Ukraine, 03115

Volyn Regional Oncology Dispensary

Lutsk, Ukraine, 43018

Lvov State Regional Oncology Medical & Diagnostic Center

Lvov, Ukraine, 79031

Ternopil State Medical Academy

Ternopil, Ukraine, 46023

United Kingdom

Royal Berkshire Hospital; Berkshire Cancer Centre

Berkshire, United Kingdom, RG1 5AN

Velindre Cancer Centre; Oncology Dept

Cardiff, United Kingdom, CF14 2TL

Cheltenham General Hospital; Gloucestershire Oncology Centre

Cheltenham, United Kingdom, GL53 7AN

Colchester General Hospital

Colchester, Essex, United Kingdom, CO4 5JL

Royal Cornwall Hospital; Dept of Clinical Oncology

Cornwall, United Kingdom, TR1 3LQ

University Hospital coventry; Oncology Department

Coventry, United Kingdom, CV2 2DX

Western General Hospital; Edinburgh Breast Unit

Edinburgh, United Kingdom, EH4 2XU

Royal Devon & Exeter Hospital; Oncology Centre

Exeter, United Kingdom, EX2 5DW

Ipswich Hospital; Oncology Pharmacy

Ipswich, United Kingdom, IP4 5PD

St James Uni Hospital; Icrf Cancer Medicine Research Unit

Leeds, United Kingdom, LS9 7TF

St. Bartholomew'S Hospital; Dept of Medical Oncology

London, United Kingdom, EC1A 7BE

UCL Hospital NHS Trust

London, United Kingdom, NW1 2PG

Royal Marsden Hospital; Dept of Med-Onc

London, United Kingdom, SW3 6JJ

Christie Hospital; Breast Cancer Research Office

Manchester, United Kingdom, M20 4QL

Mount Vernon Hospital; Centre For Cancer Treatment

Northwood, United Kingdom, HA6 2RN

Nottingham City Hospital; Oncology

Nottingham, United Kingdom, NG5 1PB

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, United Kingdom, OX3 7LJ

Peterborough City Hospital, Edith Cavell Campus; Oncology Department

Peterborough, United Kingdom, PE3 9GZ

Queen Alexandra Hospital; Haematology and Oncology Centre

Portsmouth, United Kingdom, PO6 3LY

Royal Preston Hosp; Rosemere Cancer Ctr

Preston, United Kingdom, PR2 9HT

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, United Kingdom, S10 2SJ

Uni Hospital of North Staffordshire; Staffordshire Oncology Centre

Stoke-on-Trent, United Kingdom, ST4 6QG

Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit

Sutton, United Kingdom, SM2 5PT

The Clatterbridge Cancer Ctr For Oncolgy

Wirral, United Kingdom, CH63 4JY

New Cross Hospital; Deansley Centre

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Hoffmann-La Roche

Genentech, Inc.

Breast International Group

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gelber RD, Wang XV, Cole BF, Cameron D, Cardoso F, Tjan-Heijnen V, Krop I, Loi S, Salgado R, Kiermaier A, Frank E, Fumagalli D, Caballero C, de Azambuja E, Procter M, Clark E, Restuccia E, Heeson S, Bines J, Loibl S, Piccart-Gebhart M; APHINITY Steering Committee and Investigators. Six-year absolute invasive disease-free survival benefit of adding adjuvant pertuzumab to trastuzumab and chemotherapy for patients with early HER2-positive breast cancer: A Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of the APHINITY (BIG 4-11) trial. Eur J Cancer. 2022 May;166:219-228. doi: 10.1016/j.ejca.2022.01.031. Epub 2022 Mar 18.

Bines J, Clark E, Barton C, Restuccia E, Procter M, Sonnenblick A, Fumagalli D, Parlier D, Arahmani A, Baselga J, Viale G, Reaby LL, Frank E, Gelber RD, Piccart M, Jackisch C, Petersen JA. Patient-reported function, health-related quality of life, and symptoms in APHINITY: pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer. Br J Cancer. 2021 Jul;125(1):38-47. doi: 10.1038/s41416-021-01323-y. Epub 2021 Apr 7.

Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pienkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. doi: 10.1200/JCO.20.01204. Epub 2021 Feb 4.

Bines J, Procter M, Restuccia E, Viale G, Zardavas D, Suter T, Arahmani A, Van Dooren V, Baselga J, Clark E, Eng-Wong J, Gelber RD, Piccart M, Mobus V, de Azambuja E; APHINITY Steering Committee and Investigators. Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. Clin Breast Cancer. 2020 Apr;20(2):174-181.e3. doi: 10.1016/j.clbc.2019.06.016. Epub 2019 Sep 5.

Luo Y, Li W, Jiang Z, Zhang Q, Wang L, Mao Y, Tjan-Heijnen VCG, Im SA, McConnell R, Bejarano S, Fumagalli D, Bines J, Wang B, Garg A, Kirschbrown WP, Xu B. Pharmacokinetics of pertuzumab administered concurrently with trastuzumab in Chinese patients with HER2-positive early breast cancer. Anticancer Drugs. 2019 Sep;30(8):866-872. doi: 10.1097/CAD.0000000000000808.

Kirschbrown WP, Kagedal M, Wang B, Lindbom L, Knott A, Mack R, Monemi S, Nijem I, Girish S, Freeman C, Fumagalli D, McConnell R, Jerusalem G, Twelves C, Baselga J, von Minckwitz G, Bines J, Garg A. Pharmacokinetic and exploratory exposure-response analysis of pertuzumab in patients with operable HER2-positive early breast cancer in the APHINITY study. Cancer Chemother Pharmacol. 2019 Jun;83(6):1147-1158. doi: 10.1007/s00280-019-03826-1. Epub 2019 Apr 11.

von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. doi: 10.1056/NEJMoa1703643. Epub 2017 Jun 5. Erratum In: N Engl J Med. 2017 Aug 17;377(7):702. N Engl J Med. 2018 Oct 18;379(16):1585.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01358877
• Other Study ID Numbers: BO25126; TOC4939G ( Other Identifier: Genentech ); 2010-022902-41 ( EudraCT Number ); BIG 4-11 ( Other Identifier: Breast International Group )
• First Posted: May 24, 2011
• Results First Posted: January 5, 2018
• Last Update Posted: April 10, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Docetaxel; Cyclophosphamide; Carboplatin; Doxorubicin; Fluorouracil; Trastuzumab; Epirubicin; Pertuzumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors