Trial Outcomes & Findings for Cardiac Safety Study in Patients With HER2 + Breast Cancer (NCT NCT01904903)

Results Overview

Cardiac events are defined as any of the following: * Presence of symptoms attributable to heart failure as confirmed by a cardiologist * Cardiac arrhythmia requiring pharmacological or electrical treatment * Myocardial infarction * Sudden cardiac death or death due to myocardial infarct, arrhythmia or heart failure Asymptomatic worsening of cardiac function defined as: \- Asymptomatic decline in LVEF \> 10% points from baseline and/or EF \< 35% corroborated by a confirmatory echocardiogram in 2-4 weeks Planned oncologic therapy is defined as: * In the adjuvant setting: completion of 1 year total of HER2 targeted therapy. If a patient already received part of the planned HER2 targeted therapy prior to enrollment in this trial, planned oncologic therapy will be achieved when a total of 1 year is completed. * In the metastatic setting: cessation of treating regimen due to progressive disease or non-cardiac toxicity or non-cardiac death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 18 months.

Results posted on

2022-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	HER2 Therapies, Cardiac Medications Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Overall Study STARTED	31
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	HER2 Therapies, Cardiac Medications Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Cardiac Safety Study in Patients With HER2 + Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HER2 Therapies, Cardiac Medications n=31 Participants Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	53.6 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Non-Latino Black	17 Participants n=5 Participants
Race/Ethnicity, Customized Non-Latino White	12 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 18 months.

Cardiac events are defined as any of the following: * Presence of symptoms attributable to heart failure as confirmed by a cardiologist * Cardiac arrhythmia requiring pharmacological or electrical treatment * Myocardial infarction * Sudden cardiac death or death due to myocardial infarct, arrhythmia or heart failure Asymptomatic worsening of cardiac function defined as: \- Asymptomatic decline in LVEF \> 10% points from baseline and/or EF \< 35% corroborated by a confirmatory echocardiogram in 2-4 weeks Planned oncologic therapy is defined as: * In the adjuvant setting: completion of 1 year total of HER2 targeted therapy. If a patient already received part of the planned HER2 targeted therapy prior to enrollment in this trial, planned oncologic therapy will be achieved when a total of 1 year is completed. * In the metastatic setting: cessation of treating regimen due to progressive disease or non-cardiac toxicity or non-cardiac death.

Outcome measures

Outcome measures
Measure	HER2 Therapies, Cardiac Medications n=30 Participants Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Percentage of Patients Who Complete Planned Oncologic Therapy Without the Development of a Cardiac Event or Asymptomatic Worsening of Cardiac Function.	27 Participants

SECONDARY outcome

Timeframe: Up to 18 months.

Outcome measures

Outcome measures
Measure	HER2 Therapies, Cardiac Medications n=30 Participants Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Median Time to Development of an Event Defined as Cardiac Event or Asymptomatic Worsening of Left Ventricular Dysfunction, Among Patients Who Developed One Event.	220 days Interval 201.0 to 252.5

SECONDARY outcome

Timeframe: Up to 18 months.

Difference in LVEF between end of treatment and baseline

Outcome measures

Outcome measures
Measure	HER2 Therapies, Cardiac Medications n=30 Participants Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Absolute Changes in LVEF During HER2 Targeted Therapy Between Baseline and End of Treatment	4.21 percent ejection fraction Standard Deviation 3.4

SECONDARY outcome

Timeframe: Up to 12 months.

Proportion of patients that had a hold because of symptomatic or asymptomatic cardiotoxicity. Hold is defined as any delay or discontinuation of HER2 targeted therapy due to cardiac toxicity. One cycle of HER2 targeted therapy will be considered 3 weeks. One therapy hold will be defined as any 3-week HER2 targeted therapy missed dose or 1/3 if one weekly trastuzumab dose. For patients who had a hold and resumed HER2 targeted therapy, duration of treatment hold will be described.

Outcome measures

Outcome measures
Measure	HER2 Therapies, Cardiac Medications n=30 Participants Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
HER2 Therapy Holds Attributed to Proportion of Patients With Symptomatic or Asymptomatic Cardiotoxicity.	0.1 proportion of participants

SECONDARY outcome

Timeframe: Up to 18 months.

Population: There were too few clinical events to assess correlations

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 18 months.

Population: This outcome was not analyzed. There were too few clinical events to assess correlations.

Outcome measures

Outcome data not reported

Adverse Events

HER2 Therapies, Cardiac Medications

Serious events: 3 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	HER2 Therapies, Cardiac Medications n=30 participants at risk Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks. Trastuzumab: HER2 therapy Pertuzumab: HER2 therapy Ado Trastuzumab Emtansine: HER2 therapy
Cardiac disorders Cardiac event	10.0% 3/30 • Number of events 3 • 1 year

Other adverse events

Adverse event data not reported

Additional Information

Allison Moses

MedStar

Phone: 301-256-2728

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place