Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab... | NCT00915018

Label	Type	Description	Intervention Names
neratinib plus paclitaxel	Experimental		Drug: Neratinib Drug: Paclitaxel
trastuzumab plus paclitaxel	Active Comparator		Drug: Trastuzumab Drug: Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Neratinib	Drug	Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Measure	Description	Time Frame
Progression-Free Survival	Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.	From randomization to disease progression or death, assessed up to 5.3 years

Measure	Description	Time Frame
Objective Response Rate	Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions.

Name	Affiliation	Role
Puma	Biotechnology	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ventura County Hematology-Oncology Specialists		Oxnard	California	93030	United States
Redwood Regional Medical Group

PubMed Identifier	Type	Citation	Retractions
27078022	Derived	Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. doi: 10.1001/jamaoncol.2016.0237.

ID	Title	Description
FG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

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

Defined as the interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last assessable evaluation or at the initiation of new anticancer therapy.

all randomized patients

Posted

Median

95% Confidence Interval

months

From randomization to disease progression or death, assessed up to 5.3 years

ID	Title	Description
OG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
OG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Units	Counts
Participants	OG000242 OG001237

Title

Denominators

Categories

Title	Measurements
	OG00012.9(11.1 to 14.9) OG00112.9(11.1 to 14.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.8934		Hazard Ratio (HR)	1.015			2-Sided	95	0.813	1.269					Superiority

Secondary

Objective Response Rate

Defined as the percentage of subjects who achieved confirmed tumor response (complete or partial response) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-Progressive Disease for non-target lesions, and no new lesions.

all randomized patients

Posted

Number

95% Confidence Interval

percentage of participants

From randomization to disease progression or last tumor assessment, assessed up to 5.3 years

ID	Title	Description
OG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
OG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Secondary

Duration of Response

Measured from the time at which measurement criteria were first met for CR or PR (whichever status was recorded first), until the date of first recurrence, disease progression (PD), or death was objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

patients who responded

Posted

Median

95% Confidence Interval

months

From first response to first PD or death, assessed up to 5.3 years after first subject randomized

ID	Title	Description
OG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
OG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Secondary

Clinical Benefit Rate

Defined as the proportion of patients who achieved overall tumor response (CR or PR) or SD for at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

all randomized patients

Posted

Number

95% Confidence Interval

percentage of participants

From randomization to disease progression or death, assessed up to 5.3 years

ID	Title	Description
OG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
OG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Secondary

Symptomatic or Progressive Central Nervous System (CNS) Lesions

Defined as the time interval from the date of randomization until the first date of CNS symptoms, the imaging examination shows CNS progression or is censored at the last assessable evaluation on study or prior to new anti-cancer therapy, if applicable.

If median time to Symptomatic or Progressive CNS Lesions is not estimable, cumulative incidence will be reported instead.

all randomized patients

Posted

Count of Participants

Participants

From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years

ID	Title	Description
OG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
OG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Cardiac tamponade	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Myocardial infarction	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Pericardial effusion	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Retinal degeneration	Eye disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Uveitis	Eye disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0011 affected234 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Ascites	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Dental caries	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00012 affected240 at risk EG0013 affected234 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Ileus	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0011 affected234 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Volvulus	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0007 affected240 at risk EG0011 affected234 at risk
Adhesion	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Disease progression	General disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected240 at risk EG0010 affected234 at risk
Fatigue	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Generalised oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Multi-organ failure	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Oedema peripheral	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Pyrexia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected240 at risk EG0015 affected234 at risk
Sudden death	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Swelling	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Biliary colic	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0011 affected234 at risk
Hepatitis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Contrast media allergy	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Food allergy	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Type IV hypersensitivity reaction	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Appendicitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Candida infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Catheter site cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0016 affected234 at risk
Dengue fever	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Device related infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0012 affected234 at risk
Empyema	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Furuncle	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Gastroenteritis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0003 affected240 at risk EG0010 affected234 at risk
Herpes zoster	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Pharyngitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Pleural infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Rash pustular	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Septic shock	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Sinusitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Staphylococcal infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Tooth abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0011 affected234 at risk
Urinary tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0013 affected234 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Drug administration error	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Pneumothorax traumatic	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Procedural hypotension	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Alanine aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
General physical condition abnormal	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Weight decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0012 affected234 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0007 affected240 at risk EG0011 affected234 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected240 at risk EG0010 affected234 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0011 affected234 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Benign ovarian tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0015 affected234 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Ovarian epithelial cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Ureteric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Brain oedema	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Cerebellar ischaemia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Coma	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Confusional state	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0004 affected240 at risk EG0010 affected234 at risk
Depression	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Schizophrenia	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Prerenal failure	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0012 affected234 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0012 affected234 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0012 affected234 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG0010 affected234 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Hypertension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected240 at risk EG0011 affected234 at risk
Hypotension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk
Shock	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected240 at risk EG0010 affected234 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG00075 affected240 at risk EG00165 affected234 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG00072 affected240 at risk EG00174 affected234 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG00032 affected240 at risk EG00130 affected234 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG00077 affected240 at risk EG00179 affected234 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00016 affected240 at risk EG0014 affected234 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00051 affected240 at risk EG00126 affected234 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00030 affected240 at risk EG00118 affected234 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00035 affected240 at risk EG00144 affected234 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG000222 affected240 at risk EG00178 affected234 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00031 affected240 at risk EG00120 affected234 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0004 affected240 at risk EG00112 affected234 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG000107 affected240 at risk EG00170 affected234 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00059 affected240 at risk EG00146 affected234 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00087 affected240 at risk EG00137 affected234 at risk
Asthenia	General disorders	MedDRA (17.0)	Systematic Assessment	EG00053 affected240 at risk EG00136 affected234 at risk
Fatigue	General disorders	MedDRA (17.0)	Systematic Assessment	EG00077 affected240 at risk EG00164 affected234 at risk
Influenza like illness	General disorders	MedDRA (17.0)	Systematic Assessment	EG00010 affected240 at risk EG00114 affected234 at risk
Oedema	General disorders	MedDRA (17.0)	Systematic Assessment	EG00011 affected240 at risk EG00115 affected234 at risk
Oedema peripheral	General disorders	MedDRA (17.0)	Systematic Assessment	EG00034 affected240 at risk EG00140 affected234 at risk
Pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG00113 affected234 at risk
Pyrexia	General disorders	MedDRA (17.0)	Systematic Assessment	EG00041 affected240 at risk EG00144 affected234 at risk
Cystitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG00112 affected234 at risk
Influenza	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00011 affected240 at risk EG00113 affected234 at risk
Nasopharyngitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00029 affected240 at risk EG00133 affected234 at risk
Paronychia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00016 affected240 at risk EG0019 affected234 at risk
Rhinitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 affected240 at risk EG00112 affected234 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00026 affected240 at risk EG00132 affected234 at risk
Urinary tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00017 affected240 at risk EG00115 affected234 at risk
Alanine aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG00031 affected240 at risk EG00126 affected234 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG00026 affected240 at risk EG00122 affected234 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG00015 affected240 at risk EG00111 affected234 at risk
Weight decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG00038 affected240 at risk EG00112 affected234 at risk
Weight increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0008 affected240 at risk EG00114 affected234 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG00076 affected240 at risk EG00141 affected234 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG00018 affected240 at risk EG0013 affected234 at risk
Hypercreatininaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG0012 affected234 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0009 affected240 at risk EG00116 affected234 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG00019 affected240 at risk EG0014 affected234 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG00023 affected240 at risk EG0019 affected234 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00034 affected240 at risk EG00144 affected234 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00037 affected240 at risk EG00127 affected234 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00011 affected240 at risk EG00112 affected234 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00017 affected240 at risk EG00112 affected234 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG0015 affected234 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG00118 affected234 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00031 affected240 at risk EG00132 affected234 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00030 affected240 at risk EG00125 affected234 at risk
Dizziness	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00052 affected240 at risk EG00130 affected234 at risk
Dysgeusia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00035 affected240 at risk EG00116 affected234 at risk
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00049 affected240 at risk EG00145 affected234 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00018 affected240 at risk EG00125 affected234 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00061 affected240 at risk EG00160 affected234 at risk
Paraesthesia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00021 affected240 at risk EG00112 affected234 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00047 affected240 at risk EG00153 affected234 at risk
Insomnia	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG00032 affected240 at risk EG00128 affected234 at risk
Breast pain	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0005 affected240 at risk EG00112 affected234 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00024 affected240 at risk EG00147 affected234 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00028 affected240 at risk EG00122 affected234 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00036 affected240 at risk EG00120 affected234 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00018 affected240 at risk EG00120 affected234 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0006 affected240 at risk EG00117 affected234 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG000126 affected240 at risk EG001133 affected234 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00014 affected240 at risk EG00112 affected234 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0009 affected240 at risk EG00116 affected234 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00033 affected240 at risk EG00131 affected234 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00014 affected240 at risk EG0017 affected234 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00019 affected240 at risk EG00122 affected234 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG00072 affected240 at risk EG00151 affected234 at risk
Hot flush	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG0018 affected234 at risk
Hypertension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG00013 affected240 at risk EG00119 affected234 at risk

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

ID	Term
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
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D000418	Albumins

ID	Title	Description
BG000	Neratinib + Paclitaxel	Neratinib + Paclitaxel Neratinib: Neratinib - 240 mg orally daily, administered once daily. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
BG001	Trastuzumab + Paclitaxel	Trastuzumab + Paclitaxel Trastuzumab: Trastuzumab - 4 mg/kg IV initial loading dose followed by subsequent once weekly doses of 2 mg/kg IV. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent. Paclitaxel: Paclitaxel - 80 mg/m2 IV administered on days 1, 8, and 15 of a 28-day cycle. Treatment will be administered until documented disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent.
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	Neratinib+Paclitaxel	Neratinib + Paclitaxel			67	240	239	240
EG001	Trastuzumab+Paclitaxel	Trastuzumab + Paclitaxel			56	234	230	234

ID	Term
C487932	neratinib
D000068878	Trastuzumab
D017239	Paclitaxel
D000068196	Albumin-Bound Paclitaxel