Herceptin (trastuzumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved October 1998

Specific Treatments:

metastatic breast cancer

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General Information

Herceptin (trastuzumab) is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation. HER2 is overexpressed in certain cancers.

Herceptin is specifically indicated for the following:

The 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 consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel

• as part of a treatment regimen with docetaxel and carboplatin

• as a single agent following multi-modality anthracycline based therapy.

Metastatic Breast Cancer:

• 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.

Select patients for therapy based on an FDA-approved companion diagnostic for Herceptin

Herceptin is supplied as an injection for intravenous administration. The recommended dosing is as follows:

Adjuvant Treatment of HER2-Overexpressing Breast Cancer: Administer at either: Initial dose of 4 mg/kg over 90 minute IV infusion, then 2 mg/kg over 30 minute IV infusion weekly for 12 weeks (with paclitaxel or docetaxel) or 18 weeks (with docetaxel/carboplatin). One week after the last weekly dose of Herceptin, administer 6 mg/kg as an IV infusion over 30−90 minutes every three weeks to complete a total of 52 weeks of therapy, or • Initial dose of 8 mg/kg over 90 minutes IV infusion, then 6 mg/kg over 30−90 minutes IV infusion every three weeks for 52 weeks.

Metastatic HER2-Overexpressing Breast Cancer: Initial dose of 4 mg/kg as a 90 minute IV infusion followed by subsequent weekly doses of 2 mg/kg as 30 minute IV infusions.

Clinical Results

FDA Approval

The FDA approval of Herceptin for adjuvant breast cancer was based on integrated analysis of two randomized, open-label, clinical trials (Studies 1 and 2) with a total of 4,063 women at the protocol-specified final overall survival analysis, a third randomized, open-label, clinical trial (Study 3) with a total of 3,386 women at definitive Disease-Free Survival analysis for one-year Herceptin treatment versus observation, and a fourth randomized, open-label clinical trial with a total of 3,222 patients (Study 4). In the joint analysis the Disease Free Survival rate at 3.5 years was 86.7%. 

The FDA approval of Herceptin for metastatic breast cancer was based on a randomized, controlled clinical trial in combination with chemotherapy (Study 5, n = 469 patients) and an open-label, single agent clinical trial (Study 6, n = 222 patients). Both trials studied patients with metastatic breast cancer whose tumors overexpress the HER2 protein. Study 5 data: Trial results showed that patients treated with Herceptin and chemotherapy experienced tumor progression later than patients treated with chemotherapy alone. The median time to disease progression was increased by 65 percent (from 4.6 to 7.6 months). Approximately 28 percent of women treated with Herceptin plus chemotherapy did not show evidence of tumor progression at one year compared to 14 percent of the women treated with chemotherapy alone. Study 6 data: The overall response rate assessed by the Response Evaluation Committee (REC) was 16 percent (34 of 213) with eight patients experiencing a complete response (4 percent) and 26 experiencing a partial response (12 percent). The median duration of response was 9 months.

Side Effects

Adverse effects associated with the use of Herceptin for Adjuvant Breast Cancer may include, but are not limited to, the following:

headache

diarrhea

nausea

chills

Adverse effects associated with the use of Herceptin for Metastatic Breast Cancer may include, but are not limited to, the following:

fever

chills

headache

infection

congestive heart failure

insomnia

cough

rash

The Herceptin drug label comes with the following Black Box Warning: Cardiomyopathy: Herceptin can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue Herceptin for cardiomyopathy. Infusion Reactions, Pulmonary Toxicity: Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Embryo-Fetal Toxicity: Exposure to Herceptin during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death. Advise patients of these risks and the need for effective contraception.

Mechanism of Action

Herceptin (trastuzumab) is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). HER2 is a cell membrane surface-bound receptor tyrosine kinase and is normally involved in the signal transduction pathways leading to cell growth and differentiation. HER2 is overexpressed in certain cancers.

Additional Information

For additional information regarding Herceptin or metastatic breast cancer, please visit https://www.herceptin.com/