Treatment Duration

Risk of early relapse reinforces importance of 12 months of Herceptin

12 months of Herceptin indicated regardless of patient type or dosing regimen
The risk of events is highest in the first three years after surgery²

Graph: Yearly risk of first recurrence in early breast cancer

Adapted Fig. 4 from Romond et al. Supplementary Appendix on hazard rate for first recurrence, expressed in events per 1000 women at risk per year, in the Joint Analysis.

Herceptin (trastuzumab) is administered weekly for 12 months, following completion of AC chemotherapy (doxorubicin and cyclophosphamide)
Do not administer concurrently with doxorubicin and cyclophosphamide
During the first 12 weeks, Herceptin is administered concurrently with paclitaxel
Total treatment duration, including AC chemotherapy, is 64 weeks

National Comprehensive Cancer Network^® (NCCN) guidelines recommend using Herceptin for 12 months, with cardiac monitoring³

Managing patient expectations about Herceptin-containing therapy

Share the results achieved in trials with Herceptin
Alert patients to monitoring schedule and possible side effects

Improving completion rates of planned Herceptin treatment

Lower risk of cardiac-related discontinuation
The TCH regimen eliminates the potential for anthracycline-related cardiotoxicity that may prevent Herceptin initiation
2.9% of patients in the TCH arm discontinued Herceptin due to a cardiac event compared with 5.7% of patients in the AC→TH arm¹

Higher completion rates⁴
On average, for every 100 patients receiving each regimen in BCIRG 006, 13 more were able to complete therapy with TCH

In the AC→TH arm, 2.3% of patients in the safety population* discontinued therapy prior to receiving any Herceptin
- Herceptin was initiated in 100% of patients in the safety population for the TCH arm

91.3% of patients in the AC→TH arm and 95.5% of patients in the TCH arm started Herceptin monotherapy after completion of chemotherapy
- Herceptin was discontinued during monotherapy in 10% of patients in the AC→TH arm and 5.4% of patients in the TCH arm

* Includes all patients who received at least 1 dose of study treatments.

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:
1. Herceptin Prescribing Information. Genentech, Inc. March 2009.
2. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2+ breast cancer. N Engl J Med. 2005; 353: 1673-1684 and supplementary appendix.
3. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Breast Cancer. Version 1; 2007. Available at: http://www.nccn.org. Accessed February 21, 2007.
4. Data on file. Genentech, Inc.