Study to Evaluate Exemestane With and Without Entinostat... | NCT00676663

NCT00676663

ID	Type	Description	Link
2009-012623-28	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Exemestane 25 mg + Entinostat 5 mg	Experimental	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Drug: entinostat Drug: exemestane
Exemestane 25 mg + Placebo	Placebo Comparator	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.	Drug: exemestane Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
entinostat	Drug	Entinostat 5 mg tablet orally once per week	Exemestane 25 mg + Entinostat 5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as the number of months from the date of randomization to the earlier of progressive disease (PD) or death due to any cause.	From date of randomization to discontinuation due to disease progression or death up to primary completion date (Median follow-up 6 months)

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of participants with response during treatment classified as complete response (CR) or partial response (PR), as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Other Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the number of months elapsed between the date of randomization and the date of death (whatever the cause).	First dose of study drug to end of study (Median follow-up 24 months in the EE arm and 26.4 months in the EP arm)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Postmenopausal female patients
Histologically or cytologically confirmed estrogen receptor positive (ER+) breast cancer
Relapsed or progressed on prior treatment with aromatase inhibitor (AI)
Metastatic disease must be measurable
Patients receiving palliative radiation at the non-target lesions must have a 2 week wash out period following completion of the treatment prior to enrollment
Patient may have had one prior chemotherapy as part of first line therapy as long as it was received before initiation of prior AI
Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1
Laboratory parameters: a)Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100.0 x 10^9/L; Absolute Neutrophil Count (ANC ≥) 1.5 x 10^9/L without the use of hematopoietic growth factors b)Creatinine less than 2.5 times the upper limit of normal for the institution c)Aspartate transaminase (AST) and alanine transaminase (ALT) less than 2.5 times the upper limit of normal for the institution
Able to understand and give written informed consent and comply with study procedures

Exclusion Criteria:

Relapse on treatment with non-steroidal AI after less than 12 months for patients in the adjuvant setting
Progressive disease after less than 3 months treatment with most recent AI for patients with metastatic disease
Rapidly progressive, life-threatening metastases
Any palliative radiotherapy to the measurable lesion
Previous treatment with SNDX-275 or any other histone deacetylase (HDAC) inhibitor including valproic acid
Allergy to benzamides or inactive components of the study drug
A history of allergies to any active or inactive ingredients of exemestane
Any concomitant medical condition that precludes adequate study treatment compliance
Patient is currently enrolled in (or completed within 30 days before study drug administration) another investigational drug study
Patient is currently receiving treatment with valproic acid, Zolinza (vorinostat) or any other HDAC inhibitor or deoxyribonucleic acid (DNA) methyltransferase inhibitor or any systemic anticancer treatment (with the exception of Lupron)

Contacts/Locations Module

Name	Affiliation	Role
Denise Yardley, MD	Sarah Cannon Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
California Cancer Care		Greenbrae	California		United States
Moores UCSD Cancer Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23650416	Derived	Yardley DA, Ismail-Khan RR, Melichar B, Lichinitser M, Munster PN, Klein PM, Cruickshank S, Miller KD, Lee MJ, Trepel JB. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol. 2013 Jun 10;31(17):2128-35. doi: 10.1200/JCO.2012.43.7251. Epub 2013 May 6.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Full Analysis Set included all randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
BG001	Exemestane 25 mg + Entinostat 5 mg	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0002.27(1.81 to 3.68) OG0014.28(3.26 to 5.36)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank	P-value is stratified by the randomization stratification factors and is 1-sided, with a 0.10 threshold for significance.	0.06		Hazard Ratio (HR)	0.73			2-Sided	95	0.49	1.09					Superiority

Secondary

Objective Response Rate (ORR)

ORR is defined as the percentage of participants with response during treatment classified as complete response (CR) or partial response (PR), as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Full Analysis Set included all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to discontinuation due to disease progression or intolerable Adverse Event (AE) up to primary completion date (Median follow-up 6 months)

ID	Title	Description
OG000	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
OG001	Exemestane 25 mg + Entinostat 5 mg	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.

Secondary

Clinical Benefit Rate (CBR)

CBR is defined as the percentage of participants with overall response (CR + PR) plus stable disease (SD) for 6 months as assessed by the investigator based on RECIST, version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Full Analysis Set included all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to discontinuation due to disease progression or intolerable AE up to primary completion date (Median follow-up 6 months)

ID	Title	Description
OG000	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
OG001	Exemestane 25 mg + Entinostat 5 mg	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. Abnormal clinical laboratory findings determined by the investigator to be clinically significant were recorded as AEs. A TEAE is an AE that starts after the administration of study drug.

A SAE is any AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth effect or other significant medical hazard.

Safety Population included all randomized participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

First dose to within 30 days of last dose of study drug (Up to Approximately 2 Years)

ID	Title	Description
OG000	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
OG001

Other Pre-specified

Overall Survival (OS)

OS was defined as the number of months elapsed between the date of randomization and the date of death (whatever the cause).

Full Analysis Set included all randomized participants.

Posted

Median

95% Confidence Interval

months

First dose of study drug to end of study (Median follow-up 24 months in the EE arm and 26.4 months in the EP arm)

ID	Title	Description
OG000	Exemestane 25 mg + Placebo (EP)	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.
OG001	Exemestane 25 mg + Entinostat 5 mg (EE)	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.

Units	Counts
Participants

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	Exemestane 25 mg + Placebo	Exemestane (Aromasin®) 25 mg tablets orally once daily plus a placebo-matching entinostat tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.			8	66	51	66
EG001	Exemestane 25 mg + Entinostat 5 mg	Exemestane (Aromasin®) 25 mg tablets orally once daily plus an entinostat 5 mg tablet orally once per week on Days 1, 8, 15 and 22 of each 28-day treatment cycle until development of progressive disease (PD) or unacceptable toxicity or closure of the study by the Sponsor, whichever occurred first.			10	63	58	63

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0011 affected63 at risk
Lobar pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0011 affected63 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0012 affected63 at risk
Asthenia	General disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Atrial tachycardia	Cardiac disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Constipation	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Enterocutaneous fistula	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Ileus	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Leukopenia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Pancreatic mass	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Pyrexia	General disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Sepsis	Infections and infestations	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Thrombocytopenia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0010 affected63 at risk
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Vena cava thrombosis	Vascular disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0011 affected63 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0007 affected66 at risk EG00112 affected63 at risk
Neutropenia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG00119 affected63 at risk
Thrombocytopenia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG00112 affected63 at risk
Leukopenia group	Blood and lymphatic system disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0019 affected63 at risk
Tachycardia	Cardiac disorders	MedDRA (10.1)	Systematic Assessment	EG0004 affected66 at risk EG0013 affected63 at risk
Nausea	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG00010 affected66 at risk EG00125 affected63 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0008 affected66 at risk EG00111 affected63 at risk
Constipation	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG00010 affected66 at risk EG0016 affected63 at risk
Vomiting	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG00113 affected63 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0006 affected66 at risk EG0015 affected63 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0002 affected66 at risk EG0019 affected63 at risk
Fatigue	General disorders	MedDRA (10.1)	Systematic Assessment	EG00017 affected66 at risk EG00130 affected63 at risk
Oedema peripheral	General disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG00113 affected63 at risk
Pain	General disorders	MedDRA (10.1)	Systematic Assessment	EG0004 affected66 at risk EG00110 affected63 at risk
Hot flush	General disorders	MedDRA (10.1)	Systematic Assessment	EG0006 affected66 at risk EG0015 affected63 at risk
Pyrexia	Gastrointestinal disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0014 affected63 at risk
Asthenia	General disorders	MedDRA (10.1)	Systematic Assessment	EG0004 affected66 at risk EG0013 affected63 at risk
Chills	General disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0014 affected63 at risk
Weight decreased	Investigations	MedDRA (10.1)	Systematic Assessment	EG00012 affected66 at risk EG00113 affected63 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (10.1)	Systematic Assessment	EG0005 affected66 at risk EG0015 affected63 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (10.1)	Systematic Assessment	EG0007 affected66 at risk EG0013 affected63 at risk
Alanine aminotransferase increased	Investigations	MedDRA (10.1)	Systematic Assessment	EG0006 affected66 at risk EG0013 affected63 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA (10.1)	Systematic Assessment	EG0006 affected66 at risk EG0011 affected63 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0014 affected63 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (10.1)	Systematic Assessment	EG0005 affected66 at risk EG0018 affected63 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (10.1)	Systematic Assessment	EG0002 affected66 at risk EG0016 affected63 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0014 affected63 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG00011 affected66 at risk EG00110 affected63 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG00011 affected66 at risk EG0017 affected63 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0004 affected66 at risk EG00110 affected63 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0002 affected66 at risk EG0017 affected63 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0016 affected63 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0002 affected66 at risk EG0015 affected63 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0005 affected66 at risk EG0012 affected63 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0001 affected66 at risk EG0014 affected63 at risk
Headache	Nervous system disorders	MedDRA (10.1)	Systematic Assessment	EG0007 affected66 at risk EG0019 affected63 at risk
Insomnia	Nervous system disorders	MedDRA (10.1)	Systematic Assessment	EG0007 affected66 at risk EG0017 affected63 at risk
Neuropathy	Nervous system disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0014 affected63 at risk
Anxiety	Psychiatric disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0016 affected63 at risk
Urinary tract infection	Renal and urinary disorders	MedDRA (10.1)	Systematic Assessment	EG0000 affected66 at risk EG0015 affected63 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0007 affected66 at risk EG00112 affected63 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0018 affected63 at risk
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	MedDRA (10.1)	Systematic Assessment	EG0004 affected66 at risk EG0012 affected63 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (10.1)	Systematic Assessment	EG0002 affected66 at risk EG0014 affected63 at risk
Vascular disorders	Vascular disorders	MedDRA (10.1)	Systematic Assessment	EG0003 affected66 at risk EG0018 affected63 at risk

ID	Term
D001943	Breast Neoplasms
D015674	Mammary Neoplasms, Animal

ID	Term
C118739	entinostat
C056516	exemestane

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D000820	Animal Diseases