A Study of a Combination of Trastuzumab and Capecitabine... | NCT01026142

ID	Type	Description	Link
2008-006801-17	EudraCT Number

Label	Type	Description	Intervention Names
A: Capecitabine + Trastuzumab	Active Comparator		Drug: Capecitabine Drug: Trastuzumab
B: Capecitabine + Trastuzumab + Pertuzumab	Experimental		Drug: Capecitabine Drug: Pertuzumab Drug: Trastuzumab

Name	Type	Description	Arm Group Labels	Other Names
Capecitabine	Drug	1000 mg/m2 po twice daily for 14 days every 3 weeks	B: Capecitabine + Trastuzumab + Pertuzumab

Measure	Description	Time Frame
Progression Free Survival (Independent Assessment)	Progression Free Survival (PFS) was defined as the time from randomization to first documented disease progression (PD), as determined by an Independent Review Facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. IRF review of tumor assessment ceased after the primary PFS analysis. The primary endpoint was analyzed after approximately 337 IRF-assessed PFS events were observed.	Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

Measure	Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) was defined as the time from the date of randomization to the date of death from any cause. The results of the final OS analysis are presented here. Participants who were alive or lost to follow-up at the time of the analysis were censored at the last known alive date. Participants with no postbaseline information were censored at the time of randomization plus 1 day. Prior to the final data analysis cut-off, it was ensured that all participants who were in survival follow-up had been contacted as recently as possible within the last 3 months to confirm current survival status.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Fundación Investigar		Buenos Aires		1025	Argentina
Hospital Britanico; Oncologia

ID	Title	Description
FG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
FG001	B: Capecitabine + Trastuzumab + Pertuzumab

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

Progression Free Survival (Independent Assessment)

Progression Free Survival (PFS) was defined as the time from randomization to first documented disease progression (PD), as determined by an Independent Review Facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. IRF review of tumor assessment ceased after the primary PFS analysis. The primary endpoint was analyzed after approximately 337 IRF-assessed PFS events were observed.

All randomized participants.

Posted

Median

95% Confidence Interval

months

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts
Participants	OG000224 OG001228

Title

Denominators

Categories

Title	Measurements
	OG0009.0(8 to 10) OG00111.1(9 to 13)

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	The null hypothesis for the primary endpoint is that the survival distributions of IRF-assessed PFS in the two treatment groups are the same. The alternative hypothesis is that the survival distributions of IRF-assessed PFS in the treatment and the control arms are different: H0: IRF PFS<pertuzumab> = IRF PFS<control> vs. H1: IRF PFS<pertuzumab> ≠ IRF PFS<control>	Log Rank	Two-sided and stratified by: prior CNS disease present/absent, measurable disease at baseline, and response to trastuzumab in 1L metastatic setting.	0.0731	The primary endpoint, IRF-assessed PFS, is tested at a two-sided 5% significance level.	Hazard Ratio (HR)	0.82			2-Sided	95	0.65	1.02

Secondary

Overall Survival (OS)

Overall Survival (OS) was defined as the time from the date of randomization to the date of death from any cause. The results of the final OS analysis are presented here. Participants who were alive or lost to follow-up at the time of the analysis were censored at the last known alive date. Participants with no postbaseline information were censored at the time of randomization plus 1 day. Prior to the final data analysis cut-off, it was ensured that all participants who were in survival follow-up had been contacted as recently as possible within the last 3 months to confirm current survival status.

All randomized participants.

Posted

Median

95% Confidence Interval

Months

From randomization until death from any cause (up to 7.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Secondary

Overall Survival (OS) Rate Based on a 2-year Truncated Analysis

The Overall Survival (OS) 2-year truncated analysis is the Kaplan-Meier estimate of the percentage of participants who were surviving at 2 years. OS is defined as the time from the date of randomization to the date of death from any cause, with censoring of all events and follow-up beyond the end of the second year.

All randomized participants.

Posted

Number

95% Confidence Interval

Percentage of participants

From randomization until death from any cause (up to 2 years)

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts
Participants

Secondary

Investigator Assessment Progression-Free Survival (PFS)

Investigator Assessment Progression-Free Survival (PFS) was defined as the time from randomization to the first documented progressive disease, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, or death from any cause, whichever occurred first. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

All randomized participants.

Posted

Median

95% Confidence Interval

Months

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 7.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Secondary

Time to Progression (TTP) Based Upon Independent Review Facility (IRF) Assessment

Time to Progression (TTP) was defined as time between randomization and the first occurrence of progressive disease (PD), based on IRF assessment.

All randomized participants.

Posted

Median

95% Confidence Interval

Weeks

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts
Participants

Secondary

Time to Treatment Failure (TTF) Based Upon Independent Review Facility (IRF) Assessment

Time to Treatment Failure (TTF) was defined as time between randomization and date of disease progression based on independent review, death, or withdrawal of treatment due to adverse events, withdrawn informed consent, refusal of treatment/failure to cooperate, or failure to return, whichever occurred first.

All randomized participants.

Posted

Median

95% Confidence Interval

Weeks

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts

Secondary

Overall Objective Response Rate (ORR)

Overall Objective Response Rate is based upon investigator and IRF assessments. Objective Response Rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) among those who had measurable disease at baseline. CR was defined as the disappearance of all target lesions. PR was 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.

Participants without a post-baseline tumor assessment were considered to be non-responders and were not included in this outcome measure.

Posted

Number

Percentage of participants

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Secondary

Clinical Benefit Rate (CBR)

Clinical Benefit Rate is based upon Independent Review Facility (IRF) assessments; defined as the percentage of participants a complete response (CR), partial response (PR), or stable disease for at least 8 cycles or 6 months.

Participants without a post-baseline tumor assessment were considered to be non-responders and were not included in this outcome measure.

Posted

Number

95% Confidence Interval

Percentage of participants

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts

Secondary

Duration of Objective Response

Duration of Objective Response was defined for the subpopulation of responders as time from first Independent Review Facility (IRF)-assessed complete response (CR) or partial response (PR) to subsequent first documented, IRF-confirmed evidence of disease progression. Only participants with an objective response were included in the analysis of duration of objective response.

Posted

Median

95% Confidence Interval

Weeks

Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).

ID	Title	Description
OG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
OG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0006 events6 affected218 at risk EG0018 events8 affected228 at risk
Nausea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0011 events1 affected228 at risk
Vomiting	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0011 events1 affected228 at risk
Abdominal Hernia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Colitis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Diverticulum	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Dysphagia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Gastric Perforation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Gastric Ulcer	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Ileus	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Subileus	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Left Ventricular Dysfunction	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0004 events4 affected218 at risk EG00113 events13 affected228 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0012 events2 affected228 at risk
Angina Unstable	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Arteriospasm Coronary	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Cardiac Arrest	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Supraventricular Extrasystoles	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Ventricular Fibrillation	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Femur Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0012 events2 affected228 at risk
Infusion Related Reaction	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0012 events2 affected228 at risk
Acetabulum Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Bone Fissure	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Craniocerebral Injury	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Facial Bones Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Joint Dislocation	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Lumbar Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Meniscus Injury	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Synovial Rupture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Wrist Fracture	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Sepsis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0010 events0 affected228 at risk
Appendicitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Bacteraemia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Catheter Site Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Cellulitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Clostridium Difficile Colitis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Device Related Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Phlebitis Infective	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Pneumonia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0011 events1 affected228 at risk
Pulmonary Tuberculosis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Syncope	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0011 events1 affected228 at risk
Dizziness	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0011 events1 affected228 at risk
Hemiparesis	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Ischaemic Stroke	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Sciatica	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Secondary Cerebellar Degeneration	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Status Epilepticus	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Subarachnoid Haemorrhage	Injury, poisoning and procedural complications	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0004 events4 affected218 at risk EG0014 events3 affected228 at risk
Pulmonary Thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0012 events2 affected228 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
General Physical Health Deterioration	General disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0012 events2 affected228 at risk
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0012 events2 affected228 at risk
Chest Pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Device Related Thrombosis	General disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0011 events1 affected228 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events2 affected218 at risk EG0011 events1 affected228 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0002 events1 affected218 at risk EG0010 events0 affected228 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0011 events1 affected228 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0012 events2 affected228 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Joint Swelling	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Vena Cava Thrombosis	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0012 events2 affected228 at risk
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Thrombophlebitis Superficial	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Venous Thrombosis	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0011 events1 affected228 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Acute Myeloid Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Acute Promyelocytic Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Cervix Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0011 events1 affected228 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Delirium	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Depression	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Retinal Detachment	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Anaphylactic Shock	Immune system disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Blood Sodium Decreased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Ureteric Stenosis	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk
Endometrial Hyperplasia	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0000 events0 affected218 at risk EG0011 events1 affected228 at risk
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 events1 affected218 at risk EG0010 events0 affected228 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG000275 events128 affected218 at risk EG001436 events157 affected228 at risk
Nausea	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG000152 events97 affected218 at risk EG001129 events88 affected228 at risk
Vomiting	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00056 events45 affected218 at risk EG00158 events37 affected228 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00039 events32 affected218 at risk EG00160 events41 affected228 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00036 events30 affected218 at risk EG00150 events28 affected228 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00031 events24 affected218 at risk EG00145 events29 affected228 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00023 events22 affected218 at risk EG00133 events24 affected228 at risk
Constipation	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG00027 events21 affected218 at risk EG00122 events18 affected228 at risk
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG000242 events159 affected218 at risk EG001179 events129 affected228 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00012 events11 affected218 at risk EG00145 events35 affected228 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0007 events7 affected218 at risk EG00129 events21 affected228 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00010 events9 affected218 at risk EG00117 events16 affected228 at risk
Nail Disorder	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0008 events8 affected218 at risk EG00115 events14 affected228 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00012 events11 affected218 at risk EG0016 events6 affected228 at risk
Asthenia	General disorders	MedDRA (20.0)	Systematic Assessment	EG00087 events51 affected218 at risk EG00177 events47 affected228 at risk
Fatigue	General disorders	MedDRA (20.0)	Systematic Assessment	EG00059 events39 affected218 at risk EG00162 events44 affected228 at risk
Mucosal Inflammation	General disorders	MedDRA (20.0)	Systematic Assessment	EG00036 events27 affected218 at risk EG00145 events32 affected228 at risk
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG00024 events20 affected218 at risk EG00141 events29 affected228 at risk
Oedema Peripheral	General disorders	MedDRA (20.0)	Systematic Assessment	EG00013 events13 affected218 at risk EG00119 events18 affected228 at risk
Chest Pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG00015 events12 affected218 at risk EG00111 events9 affected228 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00024 events15 affected218 at risk EG00132 events27 affected228 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00019 events17 affected218 at risk EG00127 events21 affected228 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00023 events18 affected218 at risk EG00123 events20 affected228 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00020 events12 affected218 at risk EG00121 events17 affected228 at risk
Bone Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG00016 events12 affected218 at risk EG0019 events8 affected228 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0008 events6 affected218 at risk EG00119 events12 affected228 at risk
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0007 events5 affected218 at risk EG00113 events12 affected228 at risk
Headache	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG00068 events39 affected218 at risk EG00152 events40 affected228 at risk
Dizziness	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG00028 events21 affected218 at risk EG00126 events24 affected228 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG00017 events14 affected218 at risk EG00117 events16 affected228 at risk
Paraesthesia	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG00015 events13 affected218 at risk EG0019 events9 affected228 at risk
Viral Upper Respiratory Tract Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00015 events12 affected218 at risk EG00137 events25 affected228 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00020 events17 affected218 at risk EG00128 events21 affected228 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00012 events9 affected218 at risk EG00146 events19 affected228 at risk
Paronychia	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG00015 events11 affected218 at risk EG00116 events15 affected228 at risk
Influenza	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0005 events4 affected218 at risk EG00112 events12 affected228 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG00027 events22 affected218 at risk EG00138 events30 affected228 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG00028 events24 affected218 at risk EG00125 events21 affected228 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0009 events9 affected218 at risk EG00114 events12 affected228 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG00043 events28 affected218 at risk EG00143 events36 affected228 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG00019 events13 affected218 at risk EG00140 events28 affected228 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG00089 events38 affected218 at risk EG00174 events29 affected228 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG00023 events17 affected218 at risk EG00128 events21 affected228 at risk
Weight Decreased	Investigations	MedDRA (20.0)	Systematic Assessment	EG00014 events13 affected218 at risk EG00120 events19 affected228 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG00015 events11 affected218 at risk EG00126 events17 affected228 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG00011 events8 affected218 at risk EG00124 events17 affected228 at risk
Insomnia	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG00017 events12 affected218 at risk EG00127 events23 affected228 at risk
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment	EG00018 events14 affected218 at risk EG00119 events19 affected228 at risk
Lacrimation Increased	Eye disorders	MedDRA (20.0)	Systematic Assessment	EG00017 events13 affected218 at risk EG0018 events6 affected228 at risk
Left Ventricular Dysfunction	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0005 events5 affected218 at risk EG00115 events13 affected228 at risk

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

ID	Term
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
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

ID	Title	Description
BG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
BG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A: Capecitabine + Trastuzumab	Capecitabine [Xeloda]: 1250 mg/m2 po twice daily for 14 days every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.	136	218	53	218	209	218
EG001	B: Capecitabine + Trastuzumab + Pertuzumab	Capecitabine [Xeloda]: 1000 mg/m2 po twice daily for 14 days every 3 weeks. Pertuzumab [Perjeta]: 840 mg iv loading, then 420 mg iv every 3 weeks. Trastuzumab [Herceptin]: 8 mg/kg iv loading, then 6 mg/kg iv every 3 weeks.	134	228	58	228	216	228

ID	Term
D000069287	Capecitabine
C485206	pertuzumab
D000068878	Trastuzumab