Study Evaluating Neratinib Plus Paclitaxel VS Trastuzumab Plus Paclitaxel In ErbB-2 Positive Advanced Breast Cancer (NEFERTT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00915018

Recruitment Status : Completed

First Posted : June 5, 2009

Results First Posted : November 6, 2017

Last Update Posted : August 22, 2018

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Puma Biotechnology, Inc.

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Breast Cancer
Interventions	Drug: Neratinib Drug: Trastuzumab Drug: Paclitaxel
Enrollment	479

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	242	237
Received Treatment	240	234
Completed	27	30
Not Completed	215	207
Reason Not Completed
Death	75	70
Lost to Follow-up	10	5
Withdrawal by Subject	38	27
By Sponsor due to Protocol Amendment	92	105

Baseline Characteristics

Arm/Group Title		Neratinib + Paclitaxel	Trastuzumab + Paclitaxel	Total
Arm/Group Description		Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...	Total of all reporting groups
Arm/Group Description		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.	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.	Total of all reporting groups
Overall Number of Baseline Participants		242	237	479
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	199 82.2%	193 81.4%	392 81.8%
	>=65 years	43 17.8%	44 18.6%	87 18.2%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	242 participants	237 participants	479 participants
		54.0 (11.6)	54.3 (11.0)	54.1 (11.3)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	242 participants	237 participants	479 participants
	Female	242 100.0%	237 100.0%	479 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival
Description	Defined as the interval from the date of randomization until the first...
Description	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.
Time Frame	From randomization to disease progression or death, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description:	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	242	237
Median (95% Confidence Interval) Unit of Measure: months
	12.9 (11.1 to 14.9)	12.9 (11.1 to 14.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8934
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.015
	Confidence Interval	(2-Sided) 95% 0.813 to 1.269
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Objective Response Rate
Description	Defined as the percentage of subjects who achieved confirmed tumor res...
Description	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.
Time Frame	From randomization to disease progression or last tumor assessment, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description:	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	242	237
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	74.8 (68.8 to 80.1)	77.6 (71.8 to 82.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5219
	Comments	[Not Specified]
	Method	Mantel Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.028
	Confidence Interval	(2-Sided) 95% -0.048 to 0.105
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Duration of Response
Description	Measured from the time at which measurement criteria were first met fo...
Description	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.
Time Frame	From first response to first PD or death, assessed up to 5.3 years after first subject randomized

Outcome Measure Data

Analysis Population Description

patients who responded


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description:	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	181	184
Median (95% Confidence Interval) Unit of Measure: months
	13.1 (11.1 to 15.4)	12.9 (11.0 to 15.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8431
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.974
	Confidence Interval	(2-Sided) 95% 0.752 to 1.262
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Clinical Benefit Rate
Description	Defined as the proportion of patients who achieved overall tumor respo...
Description	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.
Time Frame	From randomization to disease progression or death, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description:	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	242	237
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	88.4 (83.7 to 92.2)	85.2 (80.1 to 89.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2360
	Comments	[Not Specified]
	Method	Mantel Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.032
	Confidence Interval	(2-Sided) 95% -0.093 to 0.029
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Symptomatic or Progressive Central Nervous System (CNS) Lesions
Description	Defined as the time interval from the date of randomization until the ...
Description	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.
Time Frame	From randomization to disease progression PD or last tumor assessment, assessed up to 5.3 years

Outcome Measure Data

Analysis Population Description

all randomized patients


Arm/Group Title	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description:	Neratinib + Paclitaxel ...	Trastuzumab + Paclitaxel ...
Arm/Group Description:	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.	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.
Overall Number of Participants Analyzed	242	237
Measure Type: Count of Participants Unit of Measure: Participants
	20 8.3%	41 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neratinib + Paclitaxel, Trastuzumab + Paclitaxel
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0036
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.449
	Confidence Interval	(2-Sided) 95% 0.259 to 0.780
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From First Dose through 28 days after last dose, assessed up to 5.3 years
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Neratinib+Paclitaxel	Trastuzumab+Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
Arm/Group Description	Neratinib + Paclitaxel	Trastuzumab + Paclitaxel
All-Cause Mortality
	Neratinib+Paclitaxel	Trastuzumab+Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Neratinib+Paclitaxel	Trastuzumab+Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	67/240 (27.92%)	56/234 (23.93%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Febrile neutropenia ^† 1	1/240 (0.42%)	0/234 (0.00%)
Leukopenia ^† 1	2/240 (0.83%)	0/234 (0.00%)
Neutropenia ^† 1	1/240 (0.42%)	0/234 (0.00%)
Thrombocytopenia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Cardiac disorders
Atrial fibrillation ^† 1	0/240 (0.00%)	1/234 (0.43%)
Cardiac failure congestive ^† 1	2/240 (0.83%)	0/234 (0.00%)
Cardiac tamponade ^† 1	1/240 (0.42%)	0/234 (0.00%)
Cardio-respiratory arrest ^† 1	1/240 (0.42%)	0/234 (0.00%)
Left ventricular dysfunction ^† 1	0/240 (0.00%)	1/234 (0.43%)
Myocardial infarction ^† 1	1/240 (0.42%)	0/234 (0.00%)
Pericardial effusion ^† 1	1/240 (0.42%)	0/234 (0.00%)
Eye disorders
Retinal degeneration ^† 1	1/240 (0.42%)	0/234 (0.00%)
Uveitis ^† 1	1/240 (0.42%)	0/234 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	2/240 (0.83%)	1/234 (0.43%)
Abdominal pain upper ^† 1	1/240 (0.42%)	0/234 (0.00%)
Ascites ^† 1	2/240 (0.83%)	0/234 (0.00%)
Dental caries ^† 1	0/240 (0.00%)	1/234 (0.43%)
Diarrhoea ^† 1	12/240 (5.00%)	3/234 (1.28%)
Gastrointestinal haemorrhage ^† 1	2/240 (0.83%)	0/234 (0.00%)
Ileus ^† 1	0/240 (0.00%)	1/234 (0.43%)
Intestinal obstruction ^† 1	1/240 (0.42%)	0/234 (0.00%)
Nausea ^† 1	2/240 (0.83%)	1/234 (0.43%)
Rectal haemorrhage ^† 1	1/240 (0.42%)	0/234 (0.00%)
Small intestinal obstruction ^† 1	1/240 (0.42%)	0/234 (0.00%)
Volvulus ^† 1	1/240 (0.42%)	0/234 (0.00%)
Vomiting ^† 1	7/240 (2.92%)	1/234 (0.43%)
General disorders
Adhesion ^† 1	1/240 (0.42%)	0/234 (0.00%)
Disease progression ^† 1	3/240 (1.25%)	0/234 (0.00%)
Fatigue ^† 1	1/240 (0.42%)	1/234 (0.43%)
Generalised oedema ^† 1	1/240 (0.42%)	0/234 (0.00%)
Multi-organ failure ^† 1	0/240 (0.00%)	1/234 (0.43%)
Oedema peripheral ^† 1	1/240 (0.42%)	1/234 (0.43%)
Pyrexia ^† 1	3/240 (1.25%)	5/234 (2.14%)
Sudden death ^† 1	0/240 (0.00%)	1/234 (0.43%)
Swelling ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hepatobiliary disorders
Biliary colic ^† 1	1/240 (0.42%)	0/234 (0.00%)
Cholelithiasis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hepatic failure ^† 1	2/240 (0.83%)	1/234 (0.43%)
Hepatitis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hyperbilirubinaemia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Immune system disorders
Contrast media allergy ^† 1	0/240 (0.00%)	1/234 (0.43%)
Drug hypersensitivity ^† 1	1/240 (0.42%)	1/234 (0.43%)
Food allergy ^† 1	1/240 (0.42%)	0/234 (0.00%)
Type IV hypersensitivity reaction ^† 1	1/240 (0.42%)	0/234 (0.00%)
Infections and infestations
Appendicitis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Candida infection ^† 1	1/240 (0.42%)	0/234 (0.00%)
Catheter site cellulitis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Cellulitis ^† 1	0/240 (0.00%)	6/234 (2.56%)
Dengue fever ^† 1	0/240 (0.00%)	1/234 (0.43%)
Device related infection ^† 1	2/240 (0.83%)	2/234 (0.85%)
Empyema ^† 1	1/240 (0.42%)	0/234 (0.00%)
Furuncle ^† 1	1/240 (0.42%)	0/234 (0.00%)
Gastroenteritis ^† 1	3/240 (1.25%)	0/234 (0.00%)
Herpes zoster ^† 1	0/240 (0.00%)	1/234 (0.43%)
Infection ^† 1	1/240 (0.42%)	0/234 (0.00%)
Lower respiratory tract infection ^† 1	1/240 (0.42%)	1/234 (0.43%)
Pharyngitis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Pleural infection ^† 1	0/240 (0.00%)	1/234 (0.43%)
Pneumonia ^† 1	1/240 (0.42%)	0/234 (0.00%)
Pulmonary tuberculosis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Pyelonephritis acute ^† 1	0/240 (0.00%)	1/234 (0.43%)
Rash pustular ^† 1	1/240 (0.42%)	0/234 (0.00%)
Respiratory tract infection ^† 1	0/240 (0.00%)	1/234 (0.43%)
Septic shock ^† 1	1/240 (0.42%)	0/234 (0.00%)
Sinusitis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Staphylococcal infection ^† 1	1/240 (0.42%)	0/234 (0.00%)
Tooth abscess ^† 1	0/240 (0.00%)	1/234 (0.43%)
Upper respiratory tract infection ^† 1	2/240 (0.83%)	1/234 (0.43%)
Urinary tract infection ^† 1	0/240 (0.00%)	1/234 (0.43%)
Injury, poisoning and procedural complications
Accidental overdose ^† 1	2/240 (0.83%)	3/234 (1.28%)
Ankle fracture ^† 1	1/240 (0.42%)	0/234 (0.00%)
Drug administration error ^† 1	0/240 (0.00%)	1/234 (0.43%)
Femur fracture ^† 1	1/240 (0.42%)	0/234 (0.00%)
Intentional overdose ^† 1	1/240 (0.42%)	0/234 (0.00%)
Ligament sprain ^† 1	0/240 (0.00%)	1/234 (0.43%)
Lower limb fracture ^† 1	1/240 (0.42%)	0/234 (0.00%)
Overdose ^† 1	2/240 (0.83%)	0/234 (0.00%)
Pneumothorax traumatic ^† 1	0/240 (0.00%)	1/234 (0.43%)
Procedural hypotension ^† 1	1/240 (0.42%)	0/234 (0.00%)
Investigations
Activated partial thromboplastin time prolonged ^† 1	1/240 (0.42%)	0/234 (0.00%)
Alanine aminotransferase increased ^† 1	1/240 (0.42%)	1/234 (0.43%)
Aspartate aminotransferase increased ^† 1	1/240 (0.42%)	1/234 (0.43%)
General physical condition abnormal ^† 1	1/240 (0.42%)	0/234 (0.00%)
Weight decreased ^† 1	1/240 (0.42%)	0/234 (0.00%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	1/240 (0.42%)	2/234 (0.85%)
Dehydration ^† 1	7/240 (2.92%)	1/234 (0.43%)
Hyperglycaemia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hypokalaemia ^† 1	3/240 (1.25%)	0/234 (0.00%)
Hyponatraemia ^† 1	2/240 (0.83%)	0/234 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/240 (0.00%)	1/234 (0.43%)
Musculoskeletal chest pain ^† 1	1/240 (0.42%)	1/234 (0.43%)
Pain in extremity ^† 1	0/240 (0.00%)	1/234 (0.43%)
Rheumatoid arthritis ^† 1	1/240 (0.42%)	0/234 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour ^† 1	1/240 (0.42%)	0/234 (0.00%)
Cancer pain ^† 1	0/240 (0.00%)	1/234 (0.43%)
Gastric cancer ^† 1	1/240 (0.42%)	0/234 (0.00%)
Metastases to central nervous system ^† 1	2/240 (0.83%)	5/234 (2.14%)
Metastases to meninges ^† 1	0/240 (0.00%)	1/234 (0.43%)
Ovarian epithelial cancer ^† 1	0/240 (0.00%)	1/234 (0.43%)
Ureteric cancer ^† 1	0/240 (0.00%)	1/234 (0.43%)
Nervous system disorders
Brain oedema ^† 1	1/240 (0.42%)	0/234 (0.00%)
Cerebellar ischaemia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Coma ^† 1	1/240 (0.42%)	0/234 (0.00%)
Headache ^† 1	1/240 (0.42%)	0/234 (0.00%)
Transient ischaemic attack ^† 1	1/240 (0.42%)	0/234 (0.00%)
Psychiatric disorders
Confusional state ^† 1	4/240 (1.67%)	0/234 (0.00%)
Depression ^† 1	0/240 (0.00%)	1/234 (0.43%)
Schizophrenia ^† 1	0/240 (0.00%)	1/234 (0.43%)
Renal and urinary disorders
Prerenal failure ^† 1	1/240 (0.42%)	0/234 (0.00%)
Renal failure acute ^† 1	1/240 (0.42%)	0/234 (0.00%)
Reproductive system and breast disorders
Menorrhagia ^† 1	1/240 (0.42%)	0/234 (0.00%)
Uterine polyp ^† 1	0/240 (0.00%)	1/234 (0.43%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/240 (0.42%)	2/234 (0.85%)
Pleural effusion ^† 1	1/240 (0.42%)	2/234 (0.85%)
Pneumonia aspiration ^† 1	0/240 (0.00%)	1/234 (0.43%)
Pneumonitis ^† 1	0/240 (0.00%)	2/234 (0.85%)
Pneumothorax ^† 1	1/240 (0.42%)	0/234 (0.00%)
Pulmonary embolism ^† 1	2/240 (0.83%)	0/234 (0.00%)
Respiratory failure ^† 1	0/240 (0.00%)	1/234 (0.43%)
Skin and subcutaneous tissue disorders
Erythema ^† 1	0/240 (0.00%)	1/234 (0.43%)
Vascular disorders
Deep vein thrombosis ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hypertension ^† 1	0/240 (0.00%)	1/234 (0.43%)
Hypotension ^† 1	1/240 (0.42%)	0/234 (0.00%)
Shock ^† 1	1/240 (0.42%)	0/234 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Neratinib+Paclitaxel	Trastuzumab+Paclitaxel
	Affected / at Risk (%)	Affected / at Risk (%)
Total	239/240 (99.58%)	230/234 (98.29%)
Blood and lymphatic system disorders
Anaemia ^† 1	75/240 (31.25%)	65/234 (27.78%)
Leukopenia ^† 1	72/240 (30.00%)	74/234 (31.62%)
Lymphopenia ^† 1	32/240 (13.33%)	30/234 (12.82%)
Neutropenia ^† 1	77/240 (32.08%)	79/234 (33.76%)
Gastrointestinal disorders
Abdominal distension ^† 1	16/240 (6.67%)	4/234 (1.71%)
Abdominal pain ^† 1	51/240 (21.25%)	26/234 (11.11%)
Abdominal pain upper ^† 1	30/240 (12.50%)	18/234 (7.69%)
Constipation ^† 1	35/240 (14.58%)	44/234 (18.80%)
Diarrhoea ^† 1	222/240 (92.50%)	78/234 (33.33%)
Dyspepsia ^† 1	31/240 (12.92%)	20/234 (8.55%)
Haemorrhoids ^† 1	4/240 (1.67%)	12/234 (5.13%)
Nausea ^† 1	107/240 (44.58%)	70/234 (29.91%)
Stomatitis ^† 1	59/240 (24.58%)	46/234 (19.66%)
Vomiting ^† 1	87/240 (36.25%)	37/234 (15.81%)
General disorders
Asthenia ^† 1	53/240 (22.08%)	36/234 (15.38%)
Fatigue ^† 1	77/240 (32.08%)	64/234 (27.35%)
Influenza like illness ^† 1	10/240 (4.17%)	14/234 (5.98%)
Oedema ^† 1	11/240 (4.58%)	15/234 (6.41%)
Oedema peripheral ^† 1	34/240 (14.17%)	40/234 (17.09%)
Pain ^† 1	13/240 (5.42%)	13/234 (5.56%)
Pyrexia ^† 1	41/240 (17.08%)	44/234 (18.80%)
Infections and infestations
Cystitis ^† 1	13/240 (5.42%)	12/234 (5.13%)
Influenza ^† 1	11/240 (4.58%)	13/234 (5.56%)
Nasopharyngitis ^† 1	29/240 (12.08%)	33/234 (14.10%)
Paronychia ^† 1	16/240 (6.67%)	9/234 (3.85%)
Rhinitis ^† 1	2/240 (0.83%)	12/234 (5.13%)
Upper respiratory tract infection ^† 1	26/240 (10.83%)	32/234 (13.68%)
Urinary tract infection ^† 1	17/240 (7.08%)	15/234 (6.41%)
Investigations
Alanine aminotransferase increased ^† 1	31/240 (12.92%)	26/234 (11.11%)
Aspartate aminotransferase increased ^† 1	26/240 (10.83%)	22/234 (9.40%)
Blood alkaline phosphatase increased ^† 1	15/240 (6.25%)	11/234 (4.70%)
Weight decreased ^† 1	38/240 (15.83%)	12/234 (5.13%)
Weight increased ^† 1	8/240 (3.33%)	14/234 (5.98%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	76/240 (31.67%)	41/234 (17.52%)
Dehydration ^† 1	18/240 (7.50%)	3/234 (1.28%)
Hypercreatininaemia ^† 1	13/240 (5.42%)	2/234 (0.85%)
Hyperglycaemia ^† 1	9/240 (3.75%)	16/234 (6.84%)
Hypocalcaemia ^† 1	19/240 (7.92%)	4/234 (1.71%)
Hypokalaemia ^† 1	23/240 (9.58%)	9/234 (3.85%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	34/240 (14.17%)	44/234 (18.80%)
Back pain ^† 1	37/240 (15.42%)	27/234 (11.54%)
Bone pain ^† 1	11/240 (4.58%)	12/234 (5.13%)
Muscle spasms ^† 1	17/240 (7.08%)	12/234 (5.13%)
Musculoskeletal chest pain ^† 1	13/240 (5.42%)	5/234 (2.14%)
Musculoskeletal pain ^† 1	13/240 (5.42%)	18/234 (7.69%)
Myalgia ^† 1	31/240 (12.92%)	32/234 (13.68%)
Pain in extremity ^† 1	30/240 (12.50%)	25/234 (10.68%)
Nervous system disorders
Dizziness ^† 1	52/240 (21.67%)	30/234 (12.82%)
Dysgeusia ^† 1	35/240 (14.58%)	16/234 (6.84%)
Headache ^† 1	49/240 (20.42%)	45/234 (19.23%)
Hypoaesthesia ^† 1	18/240 (7.50%)	25/234 (10.68%)
Neuropathy peripheral ^† 1	61/240 (25.42%)	60/234 (25.64%)
Paraesthesia ^† 1	21/240 (8.75%)	12/234 (5.13%)
Peripheral sensory neuropathy ^† 1	47/240 (19.58%)	53/234 (22.65%)
Psychiatric disorders
Insomnia ^† 1	32/240 (13.33%)	28/234 (11.97%)
Reproductive system and breast disorders
Breast pain ^† 1	5/240 (2.08%)	12/234 (5.13%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	24/240 (10.00%)	47/234 (20.09%)
Dyspnoea ^† 1	28/240 (11.67%)	22/234 (9.40%)
Epistaxis ^† 1	36/240 (15.00%)	20/234 (8.55%)
Oropharyngeal pain ^† 1	18/240 (7.50%)	20/234 (8.55%)
Rhinorrhoea ^† 1	6/240 (2.50%)	17/234 (7.26%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	126/240 (52.50%)	133/234 (56.84%)
Dry skin ^† 1	14/240 (5.83%)	12/234 (5.13%)
Erythema ^† 1	9/240 (3.75%)	16/234 (6.84%)
Nail disorder ^† 1	33/240 (13.75%)	31/234 (13.25%)
Palmar-plantar erythrodysaesthesia syndrome ^† 1	14/240 (5.83%)	7/234 (2.99%)
Pruritus ^† 1	19/240 (7.92%)	22/234 (9.40%)
Rash ^† 1	72/240 (30.00%)	51/234 (21.79%)
Vascular disorders
Hot flush ^† 1	13/240 (5.42%)	8/234 (3.42%)
Hypertension ^† 1	13/240 (5.42%)	19/234 (8.12%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (17.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Senior Director, Clinical Operations
Organization:	Puma Biotechnology, Inc.
Phone:	+1 (424) 248-6500
EMail:	clinicaltrials@pumabiotechnology.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:	NCT00915018
Other Study ID Numbers:	3144A2-3005 / B1891005
First Submitted:	June 4, 2009
First Posted:	June 5, 2009
Results First Submitted:	August 10, 2017
Results First Posted:	November 6, 2017
Last Update Posted:	August 22, 2018

To Top