LUX-Breast 1: BIBW 2992 (Afatinib) in HER2-positive Metas... | NCT01125566

ID	Type	Description	Link
2009-015476-98	EudraCT Number

Label	Type	Description	Intervention Names
Arm B: trastuzumab with vinorelbine	Active Comparator	patients receive weekly intravenous infusion of trastuzumab and vinorelbine	Drug: trastuzumab Drug: vinorelbine
Arm A: BIBW 2992 with vinorelbine	Experimental	patients receive BIBW 2992 tablets once daily combined with weekly intravenous infusion of vinorelbine	Drug: BIBW 2992 Drug: vinorelbine

Name	Type	Description	Arm Group Labels	Other Names
BIBW 2992	Drug	patients receive BIBW 2992 tablets once daily and can reduce dose for adverse event management	Arm A: BIBW 2992 with vinorelbine

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered. Progression of disease was determined if at least 1 of the following criteria applied: At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm Appearance of 1 or more new lesions Unequivocal progression of existing non-target lesions	From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

Measure	Description	Time Frame
Overall Survival (OS)	OS is defined as time from randomisation to death irrespective of the cause of the death. For patients who had not died up to the cut-off date (03Sep2013), the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.	From randomisation (07Sep2010) to database lock (30Jul2018), up to 95 months.

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Achieve Clinical Research, LLC		Birmingham	Alabama	35216	United States
Ironwood Cancer and Research Centers

PubMed Identifier	Type	Citation	Retractions
26822398	Derived	Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-366. doi: 10.1016/S1470-2045(15)00540-9. Epub 2016 Jan 26.

ID	Title	Description
FG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.

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 (PFS)

PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.

Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered.

Progression of disease was determined if at least 1 of the following criteria applied:

At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm
Appearance of 1 or more new lesions
Unequivocal progression of existing non-target lesions

Randomised set (RS): The randomised set included all participants who were randomised to receive treatment, whether treated or not.

Posted

Median

Inter-Quartile Range

Months

From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

ID	Title	Description
OG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.
OG001	Trastuzumab + Vinorelbine (TV)	Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.

Units	Counts
Participants	OG000339 OG001169

Title

Denominators

Categories

Title	Measurements
	OG0005.49(3.55 to 9.07) OG0015.55(3.55 to 10.84)

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		Regression, Cox		0.4224	Two sided p-value was derived from a log rank test stratified by the setting of prior Trastuzumab failure, hormone receptors status and region of the investigational site.	Hazard Ratio (HR)	1.10				95	0.87	1.41			Hazard ratio is derived from Cox proportional hazard model stratified by prior Trastuzumab failure, hormone receptors status and region of the investigational site.		Superiority or Other

Secondary

Overall Survival (OS)

OS is defined as time from randomisation to death irrespective of the cause of the death.

For patients who had not died up to the cut-off date (03Sep2013), the date they were last known to be alive was derived from the patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date.

RS including participants with available data for OS.

Posted

Median

Inter-Quartile Range

Months

From randomisation (07Sep2010) to database lock (30Jul2018), up to 95 months.

ID	Title	Description
OG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.
OG001	Trastuzumab + Vinorelbine (TV)	Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.

Secondary

Best RECIST Assessment

Best RECIST assessment is defined as CR, PR, stable disease (SD), progressive disease (PD) or not evaluable by investigator (RECIST version 1.1).

CR for target lesions (TL): Disappearance of all target lesions.

CR for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis).

PR: At least a 30% decrease in the sum of diameters (SoD) of target lesions taking as reference the baseline sum diameters.

SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as references the smallest SoD while on study.

PD: At least a 20% increase in the SoD of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). Also, the sum must also demonstrate an absolute increase of a least 5mm. Appearance of one or more new lesions.

RS including participants with available data for best RECIST assessment.

Posted

Number

Percentage of participants

From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months

ID	Title	Description
OG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.

Secondary

Objective Response (OR)

OR is defined as complete response (CR) and partial response (PR). Assessed by investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Complete Response (CR) for target lesions (TL): Disappearance of all target lesions.

Complete Response (CR) for non-target lesions (NTL): Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10mm short axis)

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.

Other factors which add to the overall response of an imaging timepoint as PR are as below:-

CR in TL, but non-CR/Non-PD in NTL leads to PR
CR in TL, but not evaluated NTL leads to PR
PR in TL, but non-PD NTL or not all evaluated NTL leads to PR

RS including participants with available data for OR.

Posted

Number

Percentage of participants (%)

Post baseline tumour-imaging was performed at Week 8, 16, 24, 32, 40, 48, 56 and then every 12 weeks (Until final data-base lock on 30 Jul 2018; Up to 95 months)

ID	Title	Description
OG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00021 affected337 at risk EG0017 affected169 at risk EG0022 affected75 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected337 at risk EG0014 affected169 at risk EG0022 affected75 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Left ventricular failure	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Palpitations	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Pericardial effusion	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Diplopia	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Keratitis	Eye disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00021 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Gastritis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Gastroduodenitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Haemorrhagic ascites	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Ileus	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected337 at risk EG0013 affected169 at risk EG0020 affected75 at risk
Adverse drug reaction	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Catheter site inflammation	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Condition aggravated	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Device related thrombosis	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Disease progression	General disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Facial pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Gait disturbance	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
General physical health deterioration	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Mucosal inflammation	General disorders	MedDRA 21.0	Systematic Assessment	EG0005 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Non-cardiac chest pain	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected337 at risk EG0015 affected169 at risk EG0022 affected75 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Abscess intestinal	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Atypical pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Candida infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Cardiac infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Catheter site infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Cellulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0004 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Cystitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Device related infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Genital infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Hepatitis B	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Herpes zoster	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Lung infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Lymphangitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Pharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0011 affected169 at risk EG0022 affected75 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0004 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Septic shock	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0021 affected75 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Viraemia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Viral infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Wound infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Blood creatinine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Blood urea increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Neutrophil count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Platelet count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Muscle disorder	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Brain cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Breast cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG00010 affected337 at risk EG0015 affected169 at risk EG0023 affected75 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0003 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Pericardial effusion malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Altered state of consciousness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Central nervous system lesion	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Dysarthria	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Epilepsy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Gliosis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0013 affected169 at risk EG0021 affected75 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Lethargy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Migraine	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Paraparesis	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Radiculopathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Seizure	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Syncope	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Mood altered	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Dysuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Neurogenic bladder	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Proteinuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Breast mass	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Breast pain	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0010 affected169 at risk EG0021 affected75 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0014 affected169 at risk EG0021 affected75 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Breast operation	Surgical and medical procedures	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Central venous catheterisation	Surgical and medical procedures	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Aortic stenosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Phlebitis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Shock	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0011 affected169 at risk EG0020 affected75 at risk
Venous thrombosis	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG000103 affected337 at risk EG00162 affected169 at risk EG00225 affected75 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected337 at risk EG00111 affected169 at risk EG0025 affected75 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG000115 affected337 at risk EG00168 affected169 at risk EG00228 affected75 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG000256 affected337 at risk EG001139 affected169 at risk EG00246 affected75 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00040 affected337 at risk EG00116 affected169 at risk EG0021 affected75 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected337 at risk EG00114 affected169 at risk EG0025 affected75 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00035 affected337 at risk EG00127 affected169 at risk EG0026 affected75 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG000270 affected337 at risk EG00145 affected169 at risk EG0027 affected75 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00016 affected337 at risk EG00112 affected169 at risk EG0023 affected75 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00040 affected337 at risk EG0015 affected169 at risk EG0021 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG000102 affected337 at risk EG00147 affected169 at risk EG0026 affected75 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00087 affected337 at risk EG00119 affected169 at risk EG0024 affected75 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG00085 affected337 at risk EG00122 affected169 at risk EG0025 affected75 at risk
Asthenia	General disorders	MedDRA 21.0	Systematic Assessment	EG00063 affected337 at risk EG00125 affected169 at risk EG0025 affected75 at risk
Chills	General disorders	MedDRA 21.0	Systematic Assessment	EG00010 affected337 at risk EG0019 affected169 at risk EG0023 affected75 at risk
Fatigue	General disorders	MedDRA 21.0	Systematic Assessment	EG000106 affected337 at risk EG00151 affected169 at risk EG00210 affected75 at risk
Mucosal inflammation	General disorders	MedDRA 21.0	Systematic Assessment	EG00082 affected337 at risk EG00115 affected169 at risk EG0024 affected75 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG00011 affected337 at risk EG00111 affected169 at risk EG0021 affected75 at risk
Pain	General disorders	MedDRA 21.0	Systematic Assessment	EG00023 affected337 at risk EG0017 affected169 at risk EG0022 affected75 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG00074 affected337 at risk EG00132 affected169 at risk EG00211 affected75 at risk
Conjunctivitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00012 affected337 at risk EG0014 affected169 at risk EG0024 affected75 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0007 affected337 at risk EG0010 affected169 at risk EG0024 affected75 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00030 affected337 at risk EG00111 affected169 at risk EG0022 affected75 at risk
Paronychia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00063 affected337 at risk EG0012 affected169 at risk EG0022 affected75 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00032 affected337 at risk EG00127 affected169 at risk EG0028 affected75 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00035 affected337 at risk EG00115 affected169 at risk EG0024 affected75 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00024 affected337 at risk EG00116 affected169 at risk EG0027 affected75 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.0	Systematic Assessment	EG00022 affected337 at risk EG00111 affected169 at risk EG0028 affected75 at risk
Haemoglobin decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00028 affected337 at risk EG0016 affected169 at risk EG0025 affected75 at risk
Neutrophil count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00016 affected337 at risk EG00113 affected169 at risk EG0026 affected75 at risk
Weight decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00048 affected337 at risk EG00110 affected169 at risk EG0026 affected75 at risk
White blood cell count decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG00023 affected337 at risk EG0013 affected169 at risk EG0025 affected75 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00098 affected337 at risk EG00131 affected169 at risk EG0025 affected75 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG00043 affected337 at risk EG0017 affected169 at risk EG0022 affected75 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00018 affected337 at risk EG0018 affected169 at risk EG0024 affected75 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00024 affected337 at risk EG00115 affected169 at risk EG0027 affected75 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00011 affected337 at risk EG00110 affected169 at risk EG0020 affected75 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00027 affected337 at risk EG00116 affected169 at risk EG0025 affected75 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00012 affected337 at risk EG00112 affected169 at risk EG0024 affected75 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected337 at risk EG00118 affected169 at risk EG0025 affected75 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00021 affected337 at risk EG00120 affected169 at risk EG0023 affected75 at risk
Dizziness	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected337 at risk EG00118 affected169 at risk EG0025 affected75 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00047 affected337 at risk EG00125 affected169 at risk EG00210 affected75 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0009 affected337 at risk EG00111 affected169 at risk EG0022 affected75 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected337 at risk EG00116 affected169 at risk EG0023 affected75 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00015 affected337 at risk EG00111 affected169 at risk EG0022 affected75 at risk
Insomnia	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG00026 affected337 at risk EG00128 affected169 at risk EG0023 affected75 at risk
Dysuria	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG00021 affected337 at risk EG0013 affected169 at risk EG0021 affected75 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00039 affected337 at risk EG00127 affected169 at risk EG00210 affected75 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00027 affected337 at risk EG00115 affected169 at risk EG0024 affected75 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00058 affected337 at risk EG0016 affected169 at risk EG0023 affected75 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00030 affected337 at risk EG0019 affected169 at risk EG0025 affected75 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected337 at risk EG0013 affected169 at risk EG0024 affected75 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00020 affected337 at risk EG00110 affected169 at risk EG0025 affected75 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00022 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00034 affected337 at risk EG00113 affected169 at risk EG0020 affected75 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00045 affected337 at risk EG0010 affected169 at risk EG0020 affected75 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00020 affected337 at risk EG0011 affected169 at risk EG0021 affected75 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00042 affected337 at risk EG0012 affected169 at risk EG0020 affected75 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG00031 affected337 at risk EG0018 affected169 at risk EG0022 affected75 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG000160 affected337 at risk EG00119 affected169 at risk EG0028 affected75 at risk

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

ID	Term
D000577	Amides
D009930	Organic Chemicals
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
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
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D007211	Indoles
D054836	Indolizidines
D007212	Indolizines

ID	Title	Description
BG000	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.
BG001	Trastuzumab + Vinorelbine (TV)	Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.
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	Afatinib + Vinorelbine (AV)	Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.	235	337	123	337	331	337
EG001	Trastuzumab + Vinorelbine (TV)	Participants received an intravenous infusion of Trastuzumab 2 mg/kilogram (kg) weekly, following an initial loading dose of 4 mg/kg and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/m^2 on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days.	111	169	45	169	163	169
EG002	AV Switched to TV	This group describes participants who discontinued AV treatment and switched to TV, provided they were without disease progression on AV, following data monitoring committee (DMC) recommendation to terminate recruitment on 26 April 2013.	3	75	15	75	64	75

ID	Term
D000077716	Afatinib
D000068878	Trastuzumab
D000077235	Vinorelbine