Evaluation of an Anti-cancer Immunotherapy Combined With... | NCT01220128

ID	Type	Description	Link
2010-019909-42	EudraCT Number

Description Module

Detailed Description

The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.

Patients in this study will be allocated to cohorts as below. Cohort A will include postmenopausal patients with hormone receptor-positive breast cancer who receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 anti-cancer immunotherapy (WT1 ASCI)/placebo starting on Day 0. AI treatment will be administered daily for duration of either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

Cohort B will include breast cancer patients who will receive neoadjuvant chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort B will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations without trastuzumab.

Cohort C will include patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who will receive neoadjuvant trastuzumab (Herceptin) therapy combined with chemotherapy concurrently with administration of WT1 ASCI/placebo starting on Day 0. Neoadjuvant chemotherapy in Cohort C will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly or 12-weekly taxane administrations with trastuzumab.

Cohorts D and E will include patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy. For patients in these Cohorts D and E, WT1 ASCI/placebo (placebo applicable only for Cohort E patients) will be administered on Day 14 of each three-weekly cycle of chemotherapy. Neoadjuvant chemotherapy in Cohorts D and E will consist either 1) if 6 doses of WT1 ASCI/placebo: 6 cycle-treatment chemotherapy regimens consist of 6, three-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI/placebo: 8 cycle-treatment regimens consisting of 4 three-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Enrolment in Cohort E will be conditional on the absence of a safety signal and on the adequate induction of an immune response by the WT1 ASCI in Cohort D (defined as >= 40% response rate based on post-Dose 4 anti-WT1 antibody responses in at least six patients). If this criterion is met, 60 patients (40 receiving WT1 ASCI and 20 placebo) with identical eligibility criteria will be enrolled into Cohort E. In case no adequate safety and/or immunogenicity will be obtained in Cohort D, recruitment in Cohort E will not be initiated.

The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.

Label	Type	Description	Intervention Names
Cohort A-GSK2302024A Group	Experimental	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.	Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A Drug: Aromatase inhibitor
Cohort A-Placebo Group	Placebo Comparator	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.	Drug: Placebo Drug: Aromatase inhibitor Drug: 5-Fluorouracil Drug: Cyclophosphamide Drug: Docetaxel Drug: Doxorubicin Drug: Epirubicin Drug: Paclitaxel
Cohort B-GSK2302024A Group	Experimental	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.	Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A Drug: 5-Fluorouracil Drug: Cyclophosphamide Drug: Docetaxel Drug: Doxorubicin Drug: Epirubicin Drug: Paclitaxel
Cohort B-Placebo Group	Placebo Comparator

Name	Type	Description	Arm Group Labels	Other Names
GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A	Biological	6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Subjects With Severe Toxicities	Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related.	From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)
Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response	For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.	At post-GSK2302024A/placebo Dose 4 (Week 13)
Number of Patients With Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.	During the treatment period and up to 30 days post last administration

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The patient is ≥ 18 years of age at the time the informed consent to screening has been obtained.
The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy.

Isolated supraclavicular lymph node involvement is allowed.

The patient's tumor shows WT1 antigen expression.
The patient has one of the following histologically confirmed breast cancer subtypes:
- Estrogen receptor and/or progesterone positive tumor.
- Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
- HER2-negative breast cancer.
Eastern Cooperative Oncology Group (performance status of 0 or 1 at the time of study treatment allocation.
Baseline left ventricular ejection fraction of ≥ 50% as measured within six weeks prior to study treatment allocation by echocardiography or multi-gated acquisition(MUGA)scan.
The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation)::
- Hemoglobin: Within normal range according to institutional standards.
- Absolute leukocyte count: Within normal range according to institutional standards.
- Absolute lymphocyte count: Within normal range according to institutional standards.
- Platelet count: Within normal range according to institutional standards
- Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN)
- Aspartate aminotransferase: ≤ 2.5 x ULN
- Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN
- Serum creatinine: 1.5 x ULN
- Calculated creatinine clearance: > 50 mL/min
A female patient of childbearing potential may be enrolled in the study, if the patient:
- has practiced adequate contraception for 30 days prior to study product administration, and
- has a negative pregnancy test within one week prior to treatment allocation and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study product administration series.In view of the investigator, the patient can and will comply with the requirements of the protocol.
Written informed consent has been obtained from the patient prior to performance of any study specific procedure.

Exclusion Criteria:

The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
Diagnosis established by incisional biopsy.
Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol.
The patient is known to be human immunodeficiency virus -positive.
The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
The patient is known to have difficult-to-control hypertension, coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy on electrocardiogram or previous myocardial infarction or congestive heart failure.
The patient has a history of allergic reactions likely to be exacerbated by any component of the investigational product used in the study.
The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the study procedures.
The patient has received any investigational or non-registered product within 30 days preceding the first dose of study products or planned use during the study period.
The patient requires concomitant treatment with any immunosuppressive agents or with systemic corticosteroids prescribed for chronic treatment.
The patient has a significant disorder of coagulation or receives treatment with warfarin derivatives or heparin. Patients receiving individual doses of low molecular weight heparin outside of 24 hours prior to WT1-A10 + AS15 ASCI/placebo administration are eligible. Patients receiving prophylactic antiplatelet medications e.g. low-dose aspirin, and without a clinically-apparent bleeding tendency are eligible.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Newark	Delaware	19713	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
28176175	Derived	Higgins M, Curigliano G, Dieras V, Kuemmel S, Kunz G, Fasching PA, Campone M, Bachelot T, Krivorotko P, Chan S, Ferro A, Schwartzberg L, Gillet M, De Sousa Alves PM, Wascotte V, Lehmann FF, Goss P. Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study. Breast Cancer Res Treat. 2017 Apr;162(3):479-488. doi: 10.1007/s10549-017-4130-y. Epub 2017 Feb 7.

ID	Title	Description
FG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
FG001	Cohort A-Placebo Group

Arm/Group Information

ID	Title	Description
BG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
BG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
BG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.
BG003	Cohort B-Placebo Group	This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
BG004	Cohort C-GSK2302024A Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
BG005	Cohort C-Placebo Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule
BG006	Cohort D-GSK2302024A-D14 Group	This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
BG007	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Subjects With Severe Toxicities

Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related.

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.
OG003	Cohort B-Placebo Group	This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
OG004	Cohort C-GSK2302024A Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
OG005	Cohort C-Placebo Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule

Units	Counts
Participants	OG00015 OG0017 OG0029 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0021 OG003

Primary

Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response

For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration.

According-to-Protocol (ATP) Population for immunogenicity included all eligible patients who did not report major protocol deviation, who had at least received the first 4 doses of study product and provided a valid result for immunogenicity measurement within the 4 weeks following Dose 4.

Posted

Number

Subjects

At post-GSK2302024A/placebo Dose 4 (Week 13)

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group

Primary

Number of Patients With Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.

Primary

Number of Subjects With Serious Adverse Events SAE(s)

A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group

Primary

Number of Subjects With Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (CTCAE) Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5).

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Alkaline Phosphatase Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Anemia, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Aspartate Aminotransferase Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Creatine Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hemoglobin Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hypercalcemia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hyperkalemia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hypernatremia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hypoalbuminemia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hypocalcemia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hypokalemia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Hyponatremia Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and post 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Lymphocyte Count Decreased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Lymphocyte Count Increased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Neutrophil Count Decreased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Platelet Count Decreased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With White Blood Cell Decreased Abnormality, by CTCAE Maximum Grade

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Adverse Events (AEs) Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group

Primary

Number of Subjects With Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.

Primary

Number of Subjects With Serious Adverse Events (SAEs), Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period and up to 30 days post last administration

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group

Primary

Number of Subjects With Breast Cancer Pathological Response

The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.

The Total Treated Population included all patients who have received at least one dose of GSK2302024A study product or placebo.

Posted

Number

Subjects

During the treatment period, up to Week 26/32

ID	Title	Description
OG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.
OG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.
OG002	Cohort B-GSK2302024A Group

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A-GSK2302024A Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of GSK2302024A according to the treatment schedule.	0	15	3	15	15	15
EG001	Cohort A-Placebo Group	This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, according to the treatment schedule.	0	7	0	7	5	7
EG002	Cohort B-GSK2302024A Group	This group included breast cancer patients who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel, according to the treatment schedule.	1	9	4	9	9	9
EG003	Cohort B-Placebo Group	This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.	0	6	2	6	6	6
EG004	Cohort C-GSK2302024A Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of GSK2302024A, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.	0	11	5	11	11	11
EG005	Cohort C-Placebo Group	This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule	0	4	1	4	4	4
EG006	Cohort D-GSK2302024A-D14 Group	This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received GSK2302024A, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.	0	8	5	8	7	8

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG0030 events0 affected6 at risk EG004
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003
Vestibular disorder	Ear and labyrinth disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Death	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Polymyalgia rheumatica	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0021 events1 affected9 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hot flush	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG0030 events0 affected6 at risk EG0040 events0 affected11 at risk EG0050 events0 affected4 at risk EG0062 events2 affected8 at risk
Flushing	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected15 at risk EG0011 events1 affected7 at risk EG0028 events8 affected9 at risk EG003
Injection site pain	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events4 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Injection site erythema	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events5 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003
Mucosal inflammation	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Injection site reaction	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Injection site swelling	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Chills	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Injection site discomfort	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Weight decreased	Investigations	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Palpitations	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Headache	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events5 affected15 at risk EG0011 events1 affected7 at risk EG0021 events1 affected9 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0022 events2 affected9 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0026 events6 affected9 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0024 events4 affected9 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0029 events9 affected9 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected15 at risk EG0012 events2 affected7 at risk EG0022 events2 affected9 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events4 affected15 at risk EG0010 events0 affected7 at risk EG0024 events4 affected9 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0023 events3 affected9 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Gingivitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0022 events2 affected9 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0010 events0 affected7 at risk EG0020 events0 affected9 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003
Injection site haematoma	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003
Influenza	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected15 at risk EG0011 events1 affected7 at risk EG0020 events0 affected9 at risk EG003

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D047072	Aromatase Inhibitors
D005472	Fluorouracil
D003520	Cyclophosphamide
D000077143	Docetaxel
D004317	Doxorubicin
D015251	Epirubicin
D017239	Paclitaxel
D000068878	Trastuzumab

ID	Term
D065088	Steroid Synthesis Inhibitors
D004791	Enzyme Inhibitors
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D004965	Estrogen Antagonists
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D004224	Diterpenes
D013729	Terpenes
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins