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Pivotal Studies and Efficacy Data
The following four phase III trials involved more than 10,000 patients and demonstrated a significant reduction in the risk of recurrence when 12 months of Herceptin was used with standard adjuvant therapy. The trials were varied in study design and in the specific treatment regimen administered.
- The BCIRG 006 Trial
- This clinical trial, conducted by the Breast Cancer International Group (BCIRG), evaluated the efficacy and safety of 2 Herceptin-containing regimens (TCH and AC→TH) vs a control (AC→T).
- Joint Analysis of NSABP B-31 and NCCTG N9831
- Two cooperative group trials (NSABP B-31 and NCCTG N9831) with similar protocols evaluated the efficacy of adding 12 months of Herceptin to standard therapy in the adjuvant treatment of HER2+ breast cancer. Results were combined in a Joint Analysis.
- The HERA Trial
- The HERA trial, an international multicenter, randomized, open-label, controlled clinical trial conducted by the Breast International Group (BIG), evaluated the effect of 1 and 2 years of Herceptin in the adjuvant treatment of HER2+ breast cancer. The primary endpoint was disease- free survival (DFS).
- Adjuvant indications
- Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature)† breast cancer:
- As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
- With docetaxel and carboplatin
- As a single agent following multi-modality anthracycline-based therapy
† High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.
- Metastatic indications
- Herceptin is indicated:
- In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
- As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Boxed WARNINGS and Additional Important Safety Information
- Cardiotoxicity
- 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 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.
- In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.
- Herceptin can also cause asymptomatic decline in LVEF.
- Cardiac Monitoring
- Candidates for treatment with Herceptin should undergo a thorough baseline cardiac assessment, including history, physical examination, and an assessment of LVEF by echocardiogram or MUGA scan.
- Patients should undergo frequent monitoring for decreased left ventricular function during and after Herceptin treatment.
- More frequent monitoring should be employed if Herceptin is withheld in patients who develop significant left ventricular cardiac dysfunction.
- Infusion reactions and Pulmonary Toxicity
- 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
- Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia.
- In postmarketing reports, serious and fatal infusion reactions have been reported. Discontinue Herceptin in all patients with severe or life-threatening infusion reactions.
- Herceptin use can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis.
- Such events can occur as sequelae of infusion reactions.
- Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.
- Neutropenia
- Exacerbation of chemotherapy-induced neutropenia has also occurred
- In controlled clinical trials, severe neutropenia and febrile neutropenia occurred more frequently in metastatic breast cancer patients receiving Herceptin with myelosuppressive chemotherapy compared to chemotherapy alone.
- The incidence of septic death was not significantly increased.
- Pregnancy Category D
- Herceptin can cause fetal harm when administered to a pregnant woman.
- Post-marketing reports suggest that Herceptin use during pregnancy increases the risk of oligohydramnios during the second and third trimester.
- 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.
