Herceptin® (Trastuzumab)

Full Prescribing Information, including Boxed WARNINGS

Herceptin is a humanized monoclonal antibody (also called a biologic therapy). Antibodies are part of the body's normal defense against bacteria, viruses and abnormal cells such as cancer cells. Therapeutic monoclonal antibodies are created and produced in a laboratory through a complex and resource-intensive process. Their name comes from the fact that they are produced from a single cell.¹

Herceptin works on both the extracellular and the intracellular domains of the HER2 receptor:^2-5

• Continuously suppresses HER2 activity that may lead to tumor proliferation³
• Leads to cell stasis and death³
• In preclinical studies, synergy with Herceptin enhanced the effects of chemotherapy^4,6,7
• Herceptin provides constant inhibition of the HER2 receptor
  • Extended half-life enables Herceptin to maintain constant exposure

Mechanism of Action of Herceptin^3-5,8-10

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

Metastatic Indications Herceptin is indicated:

• In combination with paclitaxel for the 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

Important Safety Information Herceptin treatment can result in heart problems, including those without symptoms (reduced heart function) and those with symptoms (congestive heart failure). Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. Worsening of low white blood cell counts associated with chemotherapy has also occurred. Herceptin can cause low amniotic fluid levels and harm to the fetus when taken by a pregnant woman. The most common side effects associated with Herceptin were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain. Because everyone is different, it is not possible to predict what side effects any one person will have. Patients should talk to their doctor if they have questions or concerns about side effects.

Please see the Herceptin full prescribing information for Boxed WARNINGS and additional important safety information on http://www.herceptin.com.

Administration

• Herceptin can be administered in a physician's office.
• The recommended dose for HER2-positive metastatic breast cancer is a loading dose of 4 mg/kg of Herceptin administered over a 90-minute period and subsequent weekly infusions of 2 mg/kg administered over a 30-minute period. Herceptin is given as a weekly infusion until disease progression.
• The recommended dose for the adjuvant treatment of HER2-positive breast cancer is a loading dose of 4 mg/kg of Herceptin administered over a 90-minute period and subsequent weekly infusions of 2 mg/kg administered over a 30-minute period. Herceptin is given concurrently with paclitaxel for 12 weeks and without paclitaxel for an additional 40 weeks. Herceptin should not be administered concurrently with doxorubicin (anthracyclines) and cyclophosphamide.
• Dosing should be modified for infusion reactions and cardiomyopathy.

 

¹ Carter P, Presta L, Gorman CM, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci. 1992;89:4285-4289.

² Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999;26:60-70.

³ Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S, Arteaga CL. Herceptin-induced inhibition of phosphatidyli-nositol-3 kinase and Akt is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Research. 2002;62:4132-4141.

⁴ Arnould L, Gelly M, Penault-Llorca F. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006;94:259-267.

⁵ Bianco AR. Targeting c-erb2 and other receptors of the c-erB family: rationale and clinical applications. J Chemother. 2004;16:52-54.

⁶ Pegram MD, Konecny GE, O'Callaghan C, Beryt M, Pietras R, Slamon DJ. Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Nat Cancer Inst. 2004;96:739-749.

⁷ Baselga J, Norton L, Albanell J, Kim Y-M, Mendelsohn J. Recombinant humanized anti-HER2 antibody (HerceptinTM) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 1998;58:2825-2831.

⁸ Lewis GD, Figari I, Fendly B. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother. 1993;37:255-263.

⁹ Yarden Y. Biology of HER2 and its importance in breast cancer. Oncology. 2001;61:1-13.

¹⁰ Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene. 2000;19:6102-6114.