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Cardiac Safety Profile
Patient selection, cardiac monitoring, and treatment modifications
Patient Selection 1
- Candidates for treatment with Herceptin should undergo a thorough baseline cardiac assessment, including history, physical examination, and an assessment of left ventricular ejection fraction (LVEF) by echocardiogram or MUGA scan
Cardiac Monitoring 1
- Patients receiving Herceptin should undergo monitoring for deteriorating left ventricular function prior to Herceptin treatment, and frequently during and after Herceptin treatment
Treatment modifications for cardiac issues 1
- Discontinue Herceptin for clinically significant decreases in left ventricular function (CHF)
- In patients with asymptomatic declines in LVEF, Herceptin may be held and resumed up to three times, using the following management protocol
Treatment modifications for infusion reactions 1
- Treatment should be modified as follows for infusion reactions:
- Decrease the rate of infusion for mild or moderate infusion reactions
- Interrupt the infusion in patients with dyspnea or clinically significant hypotension
- Discontinue Herceptin for severe and life-threatening infusion reactions
In the adjuvant treatment of HER2+ breast cancer, Herceptin is generally well tolerated
Herceptin (trastuzumab) administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF).
- The incidence and severity of left ventricular cardiac dysfunction/CHF was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens
- Discontinue Herceptin treatment in patients receiving adjuvant therapy for breast cancer and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function
Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
- Herceptin can also cause asymptomatic decline in LVEF
Consistent safety profile when used sequentially with different anthracycline-based chemotherapy regimens and dosing schedules 1
*As determined by an external review committee.
† As reported by investigators.
Median durations of follow-up were:
- Joint Analysis studies: 23 months in the AC→T arm and 24 months in the AC→T+H arm
- HERA: 12.4 months in the observation arm and 12.6 months in the 1-year Herceptin arm
Cardiac risk factors 2
In NSABP B-31, a safety analysis was conducted for patients with symptoms suggestive of CHF.
Source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE) ‡
An analysis of potential risk factors for Herceptin/chemotherapy-induced CHF was conducted
‡ Defined as NYHA class III or IV CHF or possible/probable cardiac death.
Discontinuation for cardiac cause 1
Among women receiving adjuvant therapy for breast cancer in NSABP B-31, 16% discontinued Herceptin therapy due to clinical evidence of myocardial dysfunction or significant decline in LVEF.
In HERA, 2.6% of patients (44/1678) discontinued Herceptin due to cardiac toxicity.
Cardiomyopathy follow-up in the Joint Analysis 1
Among the 32 patients with clinical cardiac events, as determined by the Adjuvant Cardiac Review and Evaluation Committee (ACREC), in the Joint Analysis:
- One patient died of cardiomyopathy
- All other patients were receiving cardiac medication at last follow-up
- Approximately half of the surviving patients had recovery to a normal LVEF § on continuing medical management
The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.
Boxed WARNINGS and Additional Important Safety Information
- Cardiotoxicity and Cardiac Monitoring
- Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF).
- The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens.
- Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.
- Patients should undergo monitoring for decreased left ventricular function before Herceptin treatment, and frequently during and after Herceptin treatment.
- More frequent monitoring should be employed if Herceptin is withheld in patients who develop significant left ventricular cardiac dysfunction.
- In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.
- Infusion Reactions, Pulmonary Toxicity and Neutropenia
- Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported.
- In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension.
- Patients should be monitored until signs and symptoms completely resolve.
- Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
- Exacerbation of chemotherapy-induced neutropenia has also occurred.
Pregnancy Category D
Herceptin can cause oligohydramnios and fetal harm when administered to a pregnant woman.
Most Common Adverse Events
The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.
Please see the Herceptin full prescribing information including Boxed WARNINGS and additional important safety information.
- References:
- § Defined as > 50%.
- 1. Herceptin® (trastuzumab) Full Prescribing Information, Genentech, Inc. May 2008.
- 2. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophospahmide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005; 23:7811-7819.
