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CompletedNCT00878709ExteNETUpdated Jun 11, 2021Results posted

Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer

A Phase 3 interventional study of neratinib and placebo in Breast Cancer, sponsored by Puma Biotechnology, Inc.. Completed at 494 sites in 40 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-11.

Sponsored by Puma Biotechnology, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
2,840
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

The purpose of this study is to investigate whether neratinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer after adjuvant treatment with trastuzumab.

02

Conditions studied

  • Breast Cancer

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Keywords

  • HER-2/erbB-2 positive breast cancer
  • breast cancer
  • adjuvant therapy
  • neratinib
  • HKI-272
  • Nerlynx
  • PB-272
03

In context

Breast Neoplasms

14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.

This study's enrollment of 2,840 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Puma Biotechnology, Inc. is the lead sponsor of 38 studies on the registry; 3 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

Browse Puma Biotechnology, Inc. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Stage II through IIIC /erbB-2 positive breast cancer with node positive disease.
  • Been treated for early breast cancer with standard of care duration of trastuzumab.
  • Could have been treated neoadjuvantly but have not reached pathologic complete response.

Exclusion criteria

Exclusion Criteria:

  • Positive clinical and radiologic assessments for local or regional recurrence of disease at the time of study entry.
  • History of heart disease.
  • (QTc) interval >0.45 seconds
  • History of gastrointestinal disease with diarrhea as the major symptom.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

HER2

HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.

In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
2,840 participants (actual)

Study arms

  • Experimental
    Neratinib

    240 mg orally daily for one year

    Drug: neratinib

  • Placebo comparator
    Placebo

    orally daily for one year

    Other: placebo

Interventions

  • Drugneratinib

    Also known as: HKI-272, Nerlynx

  • Otherplacebo
06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From randomization until time of event up to 2 years

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

    Time frame: From randomization until time of event up to 2 years

Secondary outcomes

  1. Overall Survival (OS)

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

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

  2. 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.

    Time frame: From randomization until time of event up to 2 years

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

    Time frame: From randomization until time of event up to 2 years

  4. 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.

    Time frame: From randomization until time of event up to 2 years

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

    Time frame: From randomization until time of event up to 2 years

  6. 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.

    Time frame: From randomization until time of event up to 2 years

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

    Time frame: From randomization until time of event up to 2 years

  8. 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.

    Time frame: From randomization until time of event up to 2 years

  9. 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).

    Time frame: From randomization until time of event up to 2 years

Other outcomes

  1. 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.

    Time frame: From randomization until time of event up to 5 years

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

    Time frame: From randomization until time of event up to 5 years

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

    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.

    Time frame: From randomization until time of event up to 5 years

  4. 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.

    Time frame: From randomization until time of event up to 5 years

  5. 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.

    Time frame: From randomization until time of event up to 5 years

  6. 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).

    Time frame: From randomization until time of event up to 5 years

07

Results

Posted Oct 9, 2017

Participant flow

Participant flow — Overall Study
MilestoneNeratinibPlacebo
Started14201420
Completed10951183
Not completed325237
Withdrew: Withdrawal by subject197120
Withdrew: Lost to follow-up3533
Withdrew: Other reasons9384

Outcome measures

PrimaryInvasive 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.

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants with events
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2
percentage of participants with eventsNeratinibPlacebo
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 24.77.5
Statistical analysis
  • Neratinib vs Placebo · Log Rank · p = 0.008 · Hazard ratio (hr): 0.66 · 95% CI 0.49 to 0.90The 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).
PrimaryKaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms
Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants
Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms
percentage of participantsNeratinibPlacebo
Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 2 by Treatment Arms94.2 (92.6 to 95.4)91.9 (90.2 to 93.2)
SecondaryOverall Survival (OS)

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

Time frame:
Randomization until death due to any cause (up to 119 Months)
Reported as:
Number · percentage of participants
Overall Survival (OS)
percentage of participantsNeratinibPlacebo
1 Year Kaplan-Meier Estimate99.64 (99.13 to 99.85)99.43 (98.86 to 99.71)
3 Year Kaplan-Meier Estimate96.74 (95.62 to 97.57)96.44 (95.30 to 97.31)
5 Year Kaplan-Meier Estimate94.09 (92.65 to 95.25)93.26 (91.77 to 94.49)
7 Year Kaplan-Meier Estimate91.36 (89.66 to 92.79)91.29 (89.62 to 92.70)
9 Year Kaplan-Meier Estimate89.06 (86.97 to 90.84)88.65 (88.58 to 90.43)
Statistical analysis
  • Neratinib vs Placebo · Log Rank · p = 0.6914 · Hazard ratio (hr): 0.952 · 95% CI 0.747 to 1.212
SecondaryDisease-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.

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants with events
Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 2
percentage of participants with eventsNeratinibPlacebo
Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 24.78.0
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.61 · 95% CI 0.45 to 0.83The 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).
SecondaryKaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms
Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants
Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms
percentage of participantsNeratinibPlacebo
Kaplan-Meier Estimates of Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) at Year 2 by Treatment Arms94.2 (92.6 to 95.4)91.3 (89.6 to 92.7)
SecondaryDistant 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.

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants with events
Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 2
percentage of participants with eventsNeratinibPlacebo
Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 23.85.4
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.74 · 95% CI 0.52 to 1.05The 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).
SecondaryKaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms
Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants
Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms
percentage of participantsNeratinibPlacebo
Kaplan-Meier Estimates of Distant Disease-free Survival (DDFS) at Year 2 by Treatment Arms95.3 (93.9 to 96.4)94.0 (92.6 to 95.2)
SecondaryPercentage 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.

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants with events
Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 2
percentage of participants with eventsNeratinibPlacebo
Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 23.75.3
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.73 · 95% CI 0.51 to 1.04The 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).
SecondaryKaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms
Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants
Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms
percentage of participantsNeratinibPlacebo
Kaplan-Meier Estimates of Time to Distant Recurrence (TTDR) Survival at Year 2 by Treatment Arms95.5 (94.1 to 96.6)94.2 (92.8 to 95.3)
SecondaryCentral 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.

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants with events
Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 2
percentage of participants with eventsNeratinibPlacebo
Central Nervous System Recurrence in Neratinib Arm Compared to Placebo Arm at Year 20.81.1
SecondaryCumulative 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).

Time frame:
From randomization until time of event up to 2 years
Reported as:
Number · percentage of participants
Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 2
percentage of participantsNeratinibPlacebo
Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 20.92 (0.49 to 1.59)1.16 (0.68 to 1.87)
Other pre-specifiedInvasive 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.

Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants with events
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 5
percentage of participants with eventsNeratinibPlacebo
Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 58.211.5
Statistical analysis
  • Neratinib vs Placebo · Log Rank · p = 0.008 (The Log-rank test is stratified by prior trastuzumab (concurrent or sequential), nodal status (\<= 3 or \>= 4) and ER/PgR status (positive or negative).) · Hazard ratio (hr): 0.73 · 95% CI 0.57 to 0.92The 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).
Other pre-specifiedKaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms
Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants
Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms
percentage of participantsNeratinibPlacebo
Kaplan-Meier Estimates of Invasive Disease-free Survival (iDFS) at Year 5 by Treatment Arms90.2 (88.3 to 91.8)87.7 (85.7 to 89.4)
Other pre-specifiedDisease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 5

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.

Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants with events
Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 5
percentage of participants with eventsNeratinibPlacebo
Disease-free Survival Including Ductal Carcinoma in Situ (DFS-DCIS) in Neratinib Arm Compared to Placebo Arm at Year 58.512.3
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.71 · 95% CI 0.56 to 0.89The 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).
Other pre-specifiedDistant 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.

Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants with events
Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 5
percentage of participants with eventsNeratinibPlacebo
Distant Disease-free Survival (DDFS) in Neratinib Arm Compared to Placebo Arm at Year 57.09.2
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.78 · 95% CI 0.6 to 1.01The 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).
Other pre-specifiedPercentage 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.

Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants with events
Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 5
percentage of participants with eventsNeratinibPlacebo
Percentage of Participants With Time to Distant Recurrence (TTDR) Event in Neratinib Arm Compared to Placebo Arm at Year 56.88.9
Statistical analysis
  • Neratinib vs Placebo · Hazard ratio (hr): 0.79 · 95% CI 0.60 to 1.03The 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).
Other pre-specifiedCumulative 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).

Time frame:
From randomization until time of event up to 5 years
Reported as:
Number · percentage of participants
Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 5
percentage of participantsNeratinibPlacebo
Cumulative Incidence of Central Nervous System Recurrence (CNS) at Year 51.3 (0.77 to 2.06)1.82 (1.19 to 2.68)

Adverse events

Collected over From first dose through 28 days after the last dose, up to two years.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Neratinib—103/1,408 (7.3%)1,386/1,408 (98.4%)
Placebo—85/1,408 (6%)1,234/1,408 (87.6%)
Most frequent serious events
Showing 10 of 156
Most frequent serious events
EventNeratinibPlacebo
DiarrhoeaGastrointestinal disorders22/14081/1408
VomitingGastrointestinal disorders12/14081/1408
DehydrationMetabolism and nutrition disorders9/14081/1408
CellulitisInfections and infestations6/14084/1408
ErysipelasInfections and infestations5/14080/1408
NauseaGastrointestinal disorders4/14081/1408
PneumoniaInfections and infestations1/14084/1408
Alanine aminotransferase increasedInvestigations4/14080/1408
Aspartate aminotransferase increasedInvestigations4/14080/1408
FatigueGeneral disorders3/14080/1408
Most frequent other events
Showing 10 of 30
Most frequent other events
EventNeratinibPlacebo
DiarrhoeaGastrointestinal disorders1341/1408499/1408
NauseaGastrointestinal disorders605/1408303/1408
FatigueGeneral disorders381/1408283/1408
VomitingGastrointestinal disorders364/1408113/1408
Abdominal painGastrointestinal disorders339/1408144/1408
HeadacheNervous system disorders278/1408275/1408
Abdominal pain upperGastrointestinal disorders212/140896/1408
RashSkin and subcutaneous tissue disorders211/1408100/1408
Decreased appetiteMetabolism and nutrition disorders170/140840/1408
ArthralgiaMusculoskeletal and connective tissue disorders86/1408162/1408

Baseline characteristics

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

Age, Continuous
Age, Continuous(years)NeratinibPlaceboTotal
Mean52.3 ± 10.0852.3 ± 10.2852.3 ± 10.18
Sex: Female, Male
Sex: Female, Male(Participants)NeratinibPlaceboTotal
Female142014202840
Male000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)NeratinibPlaceboTotal
Asian188197385
Black or African American274774
White116511352300
Other404181
08

Study locations

494 sites
  • Anniston Oncology
    Anniston, Alabama 36207, United States
  • Birmingham Hematology and Oncology Associates, LLC
    Birmingham, Alabama 35205, United States
  • Arizona Oncology Associates, PC - HAL
    Phoenix, Arizona 85016, United States
  • Arizona Oncology Associates, PC - NAHOA
    Sedona, Arizona 86336, United States
  • Arizona Oncology Associates
    Tucson, Arizona 85704-7891, United States
  • Arizona Cancer Center
    Tucson, Arizona 85724, United States
  • Northeast Arkansas Clinic
    Jonesboro, Arkansas 72401, United States
  • Cedars-Sinai Medical Group
    Beverly Hills, California 90211, United States
  • Ronald Yanagihara, M.D.
    Gilroy, California 95020, United States
  • Glendale Adventist Medical Center Cancer Services
    Glendale, California 91206, United States
  • California Cancer Care
    Greenbrae, California 94904, United States
  • Beaver Medical Group, L.P.
    Highland, California 92346, United States
  • Breastlink Medical Group
    Long Beach, California 90806, United States
  • Long Beach Memorial Medical Center
    Long Beach, California 90806, United States
  • Facey Medical Group
    Mission Hills, California 91345, United States
  • Gynecologic Oncology Associates
    Newport Beach, California 92663, United States
  • Ventura County Hematology-Oncology Specialists
    Oxnard, California 93030, United States
  • Desert Hematology Oncology Medical Group, Inc
    Rancho Mirage, California 92270, United States
  • Helen Diller Family University of California San Francisco Comprehensive Cancer Center
    San Francisco, California 94115, United States
  • San Francisco Oncology Associates
    San Francisco, California 94115, United States
  • Redwood Regional Medical Group
    Santa Rosa, California 95403, United States
  • The Cancer Prevention and Treatment Center
    Soquel, California 95073, United States
  • Cancer Center of Central Connecticut
    Southington, Connecticut 06489, United States
  • Hematology Oncology, PC
    Stamford, Connecticut 06902, United States
  • Connecticut Oncology and Hematology
    Torrington, Connecticut 06790, United States
  • Washington Cancer Institute at Washington Hospital Center
    Washington, District of Columbia 20010, United States
  • Innovative Medical Research of South Florida, Inc.
    Aventura, Florida 33180, United States
  • University Cancer Institute, LLC
    Boynton Beach, Florida 33426, United States
  • North Broward Medical Center
    Deerfield Beach, Florida 33064, United States
  • Broward General Medical Center
    Fort Lauderdale, Florida 33316, United States
  • Florida Cancer Specialists and Research Institute
    Gainesville, Florida 32605, United States
  • Lakeland Regional Cancer Center
    Lakeland, Florida 33805, United States
  • Hematology Oncology Associates
    Loxahatchee Groves, Florida 33470, United States
  • Florida Cancer Affiliates - Ocala
    Ocala, Florida 34471, United States
  • Mid-Florida Hematology & Oncology Centers, PA
    Orange City, Florida 32763-8316, United States
  • Cancer Centers of Florida
    Orlando, Florida 32806, United States
  • M.D. Anderson Cancer Center Orlando
    Orlando, Florida 32806, United States
  • Florida Cancer Research Institute
    Plantation, Florida 33324, United States
  • Hematology Oncology Associates of Treasure Coast
    Port Saint Lucie, Florida 34592, United States
  • Florida Cancer Specialists, P.L.
    Saint Petersburg, Florida 33705, United States
  • Oncology and Hematology of West Broward
    Tamarac, Florida 33321, United States
  • Florida Medical Clinic, P.A.
    Zephyrhills, Florida 33542, United States
  • Phoebe Cancer Center
    Albany, Georgia 31701, United States
  • Piedmont Cancer Institute
    Atlanta, Georgia 30318, United States
  • Augusta Oncology Associates (ACORN), P.C.
    Augusta, Georgia 30909, United States
  • Dwight David Eisenhower Army Medical Center
    Fort Gordon, Georgia 30905-5650, United States
  • Straub Clinic & Hospital
    Honolulu, Hawaii 96813-3083, United States
  • Portneuf Medical Center
    Pocatello, Idaho 83201, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • Cancer Care Specialists of Illinois, Decatur Memorial Hospital Clinical Research
    Decatur, Illinois 62526, United States
  • Midwest Center for Hematology/Oncology
    Joliet, Illinois 60432, United States
  • Medical Arts Associates, Ltd
    Moline, Illinois 61265, United States
  • Advocate Medical Group
    Niles, Illinois 60714, United States
  • Cancer Care & Hematology Specialists of Chicagoland
    Niles, Illinois 60714, United States
  • Quincy Medical Group, Cancer Center at Blessing Hospital
    Quincy, Illinois 62301, United States
  • North Shore Cancer Research Associates
    Skokie, Illinois 60076, United States
  • Orchard Healthcare Research, Inc.
    Skokie, Illinois 60076, United States
  • Orchard Research, LLC
    Skokie, Illinois 60076, United States
  • Simmons Cancer Institute
    Springfield, Illinois 62702, United States
  • Springfield Clinic, LLP
    Springfield, Illinois 62702, United States
  • Midwestern Regional Medical Center
    Zion, Illinois 60099, United States
  • Central Indiana Cancer Centers
    Indianapolis, Indiana 46219, United States
  • Hematology Oncology of Indiana
    Indianapolis, Indiana 46260-2082, United States
  • Community Hospital
    Munster, Indiana 46321, United States
  • Ashland-Bellefonte Cancer Center
    Ashland, Kentucky 41101-7016, United States
  • Purchase Cancer Group
    Paducah, Kentucky 42001, United States
  • Hematology-Oncology Clinic
    Baton Rouge, Louisiana 70809, United States
  • Crescent City Research Consortium, LLC
    Marrero, Louisiana 70072, United States
  • Central Maine Healthcare Corp
    Lewiston, Maine 04240, United States
  • Mercy Hospital Oncology/Hematology Center
    Portland, Maine 04102, United States
  • York Hospital Oncology Treatment Center
    York, Maine 03909, United States
  • Medical Oncology & Hematology Mercy Medical Center
    Baltimore, Maryland 21202, United States
  • Harry and Jeanette Weinberg Cancer Center
    Baltimore, Maryland 21237, United States
  • Alliance Hematology Oncology, PA Carroll County Cancer Center
    Westminster, Maryland 21157, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Massachusetts General Hospital - Gillette Center
    Boston, Massachusetts 02215, United States
  • University of Massachusetts Memorial Medical Center
    Worcester, Massachusetts 01655, United States
  • Barbara Ann Karmanos Cancer Institute
    Detroit, Michigan 48201-2013, United States
  • Cancer and Hematology Centers of Western Michigan
    Grand Rapids, Michigan 49503, United States
  • Medical Specialty Associates
    Grand Rapids, Michigan 49503, United States
  • Northern Michigan Hematology/Oncology
    Petoskey, Michigan 49770, United States
  • Minnesota Oncology Hematology, PA
    Minneapolis, Minnesota 55404, United States
  • Park Nicollet Institute
    Saint Louis Park, Minnesota 55426, United States
  • North Mississippi Hematology and Oncology Associates, Ltd.
    Tupelo, Mississippi 38801, United States
  • Capitol Comprehensive Cancer Care Clinic
    Jefferson City, Missouri 65109, United States
  • St. Joseph's Oncology
    Saint Joseph, Missouri 64507, United States
  • Washington University School of Medicine Siteman Cancer Center
    Saint Louis, Missouri 63110, United States
  • Mercy Medical Research Institute
    Springfield, Missouri 65807, United States
  • Montana Cancer Specialists
    Missoula, Montana 59802, United States
  • Southeast Nebraska Hematology & Oncology Consultants, PC
    Lincoln, Nebraska 68510, United States
  • Great Plains Regional Medical Center
    North Platte, Nebraska 69101, United States
  • The Center for Cancer and Hematologic Disease
    Cherry Hill, New Jersey 08003, United States
  • Trinitas Comprehensive Cancer Center
    Elizabeth, New Jersey 07207, United States
  • Saint Barnabas Health Care System
    Livingston, New Jersey 07039, United States
  • Summit Medical Group
    Morristown, New Jersey 07960, United States
  • Oncology and Hematology Specialist
    Mountain Lakes, New Jersey 07046, United States
  • Jersey Shore University Medical Center
    Neptune, New Jersey 07754, United States
  • The Valley Hospital, Luckow Pavilion
    Paramus, New Jersey 07652, United States
  • Cooper University Hospital
    Voorhees, New Jersey 08043-4689, United States
  • Eastchester Center for Cancer Care
    Bronx, New York 10469, United States

Showing the first 100 of 494 sites across 40 countries. Choose a country and city above to see the rest.

09

References and documents

Publications

  • Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, Chiu J, Ohtani S, Takahashi M, Miyaki T, Lu YS, Xu B, Yap YS, Bustam A, Yao B, Zhang B, Bryce R, Chan A. Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer. Future Oncol. 2019 Jul;15(21):2489-2501. doi: 10.2217/fon-2019-0143. Epub 2019 May 29. PubMed 31140297 ↗
  • Chia SKL, Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Kim SB, Jakobsen EH, Harvey V, Robert N, Smith J 2nd, Harker G, Zhang B, Eli LD, Ye Y, Lalani AS, Buyse M, Chan A. PIK3CA alterations and benefit with neratinib: analysis from the randomized, double-blind, placebo-controlled, phase III ExteNET trial. Breast Cancer Res. 2019 Mar 11;21(1):39. doi: 10.1186/s13058-019-1115-2. PubMed 30867034 ↗
  • Mortimer J, Di Palma J, Schmid K, Ye Y, Jahanzeb M. Patterns of occurrence and implications of neratinib-associated diarrhea in patients with HER2-positive breast cancer: analyses from the randomized phase III ExteNET trial. Breast Cancer Res. 2019 Feb 27;21(1):32. doi: 10.1186/s13058-019-1112-5. PubMed 30813966 ↗
  • Delaloge S, Cella D, Ye Y, Buyse M, Chan A, Barrios CH, Holmes FA, Mansi J, Iwata H, Ejlertsen B, Moy B, Chia SKL, Gnant M, Smichkoska S, Ciceniene A, Martinez N, Filipovic S, Ben-Baruch NE, Joy AA, Langkjer ST, Senecal F, de Boer RH, Moran S, Yao B, Bryce R, Auerbach A, Fallowfield L, Martin M. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann Oncol. 2019 Apr 1;30(4):567-574. doi: 10.1093/annonc/mdz016. PubMed 30689703 ↗
  • Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomasevic Z, Denduluri N, Separovic R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. doi: 10.1016/S1470-2045(17)30717-9. Epub 2017 Nov 13. PubMed 29146401 ↗
  • Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SKL, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-377. doi: 10.1016/S1470-2045(15)00551-3. Epub 2016 Feb 10. PubMed 26874901 ↗

Individual participant data

Plan to share: Yes — Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.

Access criteria: Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest. Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.

Data sharing details ↗ · pumabiotechnology.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 11, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00878709
Lead sponsor
Puma Biotechnology, Inc.
Responsible party
Sponsor
First posted
Apr 9, 2009
Start date
Jul 9, 2009
Primary completion
Aug 21, 2014
Completion
Oct 4, 2019
Results posted
Oct 9, 2017
Last update
Jun 11, 2021

Study contacts

Senior Vice President Clinical Science and Pharmacology
study director · Puma Biotechnology, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Neratinib

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