Study Evaluating The Effects Of Neratinib After Adjuvant... | NCT00878709

Label	Type	Description	Intervention Names
Neratinib	Experimental	240 mg orally daily for one year	Drug: neratinib
Placebo	Placebo Comparator	orally daily for one year	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
neratinib	Drug		Neratinib	HKI-272 Nerlynx
placebo

Measure	Description	Time Frame
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2	Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.	From randomization until time of event up to 2 years
Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms		From randomization until time of event up to 2 years

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause, censored at the last date known alive.	Randomization until death due to any cause (up to 119 Months)
Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2

Measure	Description	Time Frame
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 5	Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.	From randomization until time of event up to 5 years

Name	Affiliation	Role
Senior Vice President Clinical Science and Pharmacology	Puma Biotechnology, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Anniston Oncology		Anniston	Alabama	36207	United States
Birmingham Hematology and Oncology Associates, LLC

PubMed Identifier	Type	Citation	Retractions
36898233	Derived	Holmes FA, Moy B, Delaloge S, Chia SKL, Ejlertsen B, Mansi J, Iwata H, Gnant M, Buyse M, Barrios CH, Silovski T, Separovic R, Bashford A, Zotano AG, Denduluri N, Patt D, Gokmen E, Gore I, Smith JW 2nd, Loibl S, Masuda N, Tomasevic Z, Petrakova K, DiPrimeo D, Wong A, Martin M, Chan A; ExteNET Study Group. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. Eur J Cancer. 2023 May;184:48-59. doi: 10.1016/j.ejca.2023.02.002. Epub 2023 Feb 10.
31140297

ID	Title	Description
FG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
FG001

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

Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2

Invasive disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants	OG0001420 OG0011420

Title

Denominators

Categories

Title	Measurements
	OG0004.7 OG0017.5

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	Invasive disease-free survival (iDFS) in neratinib arm compared to placebo arm.	Log Rank	The Log-rank test is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).	0.008		Hazard Ratio (HR)	0.66			2-Sided	95	0.49	0.90			The hazard ratio is estimated by stratified Cox model. The Cox model is stratified by prior trastuzumab (concurrent or sequential), nodal status (<= 3 or >= 4) and ER/PgR status (positive or negative).		Superiority

Primary

Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Secondary

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause, censored at the last date known alive.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

Randomization until death due to any cause (up to 119 Months)

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year.Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Secondary

Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2

Disease-free survival including DCIS time is defined as the time from date of randomization until the first occurrence of DCIS or an iDFS event (an iDFS event including invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, or distant recurrence and death from any.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Secondary

Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Secondary

Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 2

Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts

Secondary

Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Secondary

Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 2

Percentage of Participants with TTDR events is reported. TTDR is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units

Secondary

Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Secondary

Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 2

CNS recurrence is defined as the time from randomization to CNS as the first distant recurrence. Competing events include distant recurrence at other sites as the first distant recurrence and death from any cause prior to distant recurrence.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Secondary

Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2

Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray's method (Gray,1988).

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 2 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Other Pre-specified

Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 5

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Other Pre-specified

Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Other Pre-specified

Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 5

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Other Pre-specified

Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 5

Distant disease-free survival time is defined as the time from date of randomization until the first occurrence of distant recurrence or death from any cause.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts

Other Pre-specified

Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 5

Percentage of Participants with TTDR events is reported. TTDR is defined as the time from date of randomization until the first occurrence of distant recurrence or death from breast cancer.

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

percentage of participants with events

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Other Pre-specified

Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 5

Cumulative incidence of Central Nervous System Recurrence (CNS) is estimated by Gray's method (Gray,1988).

Intent to treat (ITT) population included all participants who were randomized regardless of whether they received any study treatment.

Posted

Number

95% Confidence Interval

percentage of participants

From randomization until time of event up to 5 years

ID	Title	Description
OG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
OG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Angina pectoris	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Myocardial infarction	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Tachycardia	Cardiac disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00022 affected1,408 at risk EG0011 affected1,408 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00012 affected1,408 at risk EG0011 affected1,408 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0004 affected1,408 at risk EG0011 affected1,408 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0010 affected1,408 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0011 affected1,408 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Abdominal strangulated hernia	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Enterocele	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Rectal cancer	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Colitis	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0012 affected1,408 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Fatigue	General disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected1,408 at risk EG0010 affected1,408 at risk
Non-cardiac chest pain	General disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected1,408 at risk EG0010 affected1,408 at risk
Pyrexia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0011 affected1,408 at risk
Asthenia	General disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0010 affected1,408 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Food allergy	Immune system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0006 affected1,408 at risk EG0014 affected1,408 at risk
Erysipelas	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0005 affected1,408 at risk EG0010 affected1,408 at risk
Bronchitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0011 affected1,408 at risk
Anal abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Anorectal cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Appendicitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Appendicitis perforated	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Breast cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Cystitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Escherichia urinary tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Gastroenteritis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Gastroenteritis salmonella	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Herpes zoster	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Localised infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Ophthalmic herpes zoster	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0014 affected1,408 at risk
Rectal abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Streptococcal sepsis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Viral infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Abdominal wall abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Breast abscess	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Device related infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0013 affected1,408 at risk
Diverticulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Incision site cellulitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Mastitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Septic shock	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Multiple injuries	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Sternal fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0012 affected1,408 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Alanine aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0004 affected1,408 at risk EG0010 affected1,408 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0004 affected1,408 at risk EG0010 affected1,408 at risk
Blood creatine increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Staphylococcus test positive	Investigations	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Ejection fraction decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0009 affected1,408 at risk EG0011 affected1,408 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0012 affected1,408 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Benign female reproductive tract neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Glioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Benign breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0012 affected1,408 at risk
Breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Metastases to eye	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Sarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Sarcoma uterus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Vascular neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Syncope	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected1,408 at risk EG0012 affected1,408 at risk
Ageusia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Anosmia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Cerebral infarction	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Paresis	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Brain oedema	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Dizziness	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Intercostal neuralgia	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Speech disorder	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Tremor	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Mental status changes	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0010 affected1,408 at risk
Depression	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0012 affected1,408 at risk
Anxiety	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Mental disorder	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected1,408 at risk EG0010 affected1,408 at risk
Renal failure	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0010 affected1,408 at risk
Hyperuricosuria	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Renal colic	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Bladder prolapse	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Endometrial hyperplasia	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Endometrial hypertrophy	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Vulval leukoplakia	Reproductive system and breast disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0003 affected1,408 at risk EG0013 affected1,408 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0002 affected1,408 at risk EG0011 affected1,408 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Skin necrosis	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0011 affected1,408 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hysterosalpingo-oophorectomy	Surgical and medical procedures	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hypotension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0001 affected1,408 at risk EG0010 affected1,408 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk
Hypertension	Vascular disorders	MedDRA (17.0)	Systematic Assessment	EG0000 affected1,408 at risk EG0011 affected1,408 at risk

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

ID	Title	Description
BG000	Neratinib	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
BG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.
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	Patients who completed prior adjuvant trastuzumab received six 40 mg neratinib tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.			103	1,408	1,386	1,408
EG001	Placebo	Patients who completed prior adjuvant trastuzumab received six 40 mg placebo tablets (240 mg) taken orally once daily with food, preferably in the morning, continuously for one year. Therapy continued until unacceptable toxicity, recurrent disease, death, or withdrawal of consent occurred.			85	1,408	1,234	1,408