See Boxed WARNINGS and Additional Important Safety Information

Adjuvant breast cancer 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 breast cancer 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

Metastatic gastric cancer indication

Herceptin is indicated, in combination with cisplatin and capecitabine or 5 fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Boxed WARNINGS

Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy.
Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of Herceptin. Discontinue Herceptin for cardiomyopathy.
Herceptin can result in serious and fatal infusion reactions and pulmonary toxicity. Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Please see full prescribing information for Boxed WARNINGS and additional important safety information.

Joint Analysis of NSABP B-31 and NCCTG

Two cooperative group phase 3 trials with similar protocols evaluated the efficacy and safety of adding 1 year of Herceptin to adjuvant chemotherapy in the treatment of HER2+ breast cancer¹
- Results were combined in a Joint Analysis
Patients (N=3752) were randomized to receive 1 of the following regimens¹:
- AC→TH: doxorubicin and cyclophosphamide followed by paclitaxel plus Herceptin
- AC→T: doxorubicin and cyclophosphamide followed by paclitaxel
Hormonal therapy was administered concurrently with Herceptin to patients with ER+ and/or PR+ breast cancer (as appropriate)¹
Radiation therapy was given concurrently with Herceptin (after completion of chemotherapy) as appropriate¹

*In NCCTG N9831, there was a sequential third arm that was not analyzed as part of the Joint Analysis.

Joint Analysis showed that 1 year of Herceptin significantly improved DFS1

Herceptin plus chemotherapy reduced the risk of disease recurrence by 52%²

At 3.5 years, absolute risk of disease recurrence was decreased by 15.3% in the Herceptin-containing regimen compared with AC→T (95% CI: 11.9%-18.6%)²
Benefit of 1 year of Herceptin was consistent with that seen in HERA¹

Boxed WARNINGS and Additional Important Safety Information

Cardiomyopathy and Cardiac Monitoring
Herceptin administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving Herceptin with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy.
Discontinue Herceptin treatment in patients receiving adjuvant breast cancer therapy and withhold Herceptin in patients with metastatic disease for clinically significant decrease in left ventricular function.
Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of Herceptin.
Monitor frequently for decreased left ventricular function during and after Herceptin treatment. Monitor more frequently if Herceptin is withheld for significant left ventricular cardiac dysfunction.

Infusion Reactions and Pulmonary Toxicity
Herceptin administration can result in serious and fatal infusion reactions and pulmonary toxicity.
Symptoms usually occur during or within 24 hours of Herceptin administration.
Interrupt Herceptin infusion for dyspnea or clinically significant hypotension.
Monitor patients until symptoms completely resolve.
Discontinue Herceptin for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Embryo-Fetal Toxicity
Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Advise women of the potential hazard to the fetus resulting from Herceptin exposure during pregnancy and provide contraception counseling to women of childbearing potential.

Exacerbation of Chemotherapy-Induced Neutropenia
In randomized, controlled clinical trials, the per-patient incidences of NCI CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone.

HER2 Testing
Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown.

Most Common Adverse Reactions
The most common adverse reactions associated with Herceptin in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.
The most common adverse reactions associated with Herceptin in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.

Please see the Herceptin full Prescribing Information including Boxed WARNINGS and additional important safety information.

References:
1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.
2. Data on file. Genentech, Inc.

1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010. [LINK TO PI] 2. Data on file. Genentech, Inc.

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