Adjuvant Breast Cancer
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
- 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.
Herceptin is indicated:
Metastatic Gastric Cancer
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 and Additional Important Safety Information
- 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.
- Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling
cardiac failure, cardiomyopathy, and cardiac death.
- Herceptin can also cause asymptomatic decline in LVEF.
- 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.
- Conduct thorough cardiac assessment, including history, physical examination, and determination
of LVEF by echocardiogram or MUGA scan.
- Monitor frequently for decreased left ventricular function during and after Herceptin
- Monitor more frequently if Herceptin is withheld for significant left ventricular cardiac
- Herceptin administration can result in serious and fatal infusion reactions.
- 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 infusion reactions manifesting as anaphylaxis, angioedema,
interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent
discontinuation in all patients with severe infusion reactions.
- 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.
- Exposure to Herceptin during pregnancy can result in oligohydramnios and oligohydramnios
sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal
- Advise women of the potential hazard to the fetus resulting from Herceptin exposure during
pregnancy and provide counseling to women of childbearing potential to use effective
contraceptive methods during treatment and for a minimum of six months following Herceptin.
- Advise nursing mothers treated with Herceptin to discontinue nursing or discontinue Herceptin,
taking into account the importance of the drug to the mother.
- Encourage women who are exposed to Herceptin during pregnancy to enroll in the MotHER Pregnancy Registry
by calling 1-800-690-6720.
- Herceptin administration 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.
- Discontinue Herceptin in patients experiencing pulmonary toxicity.
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. The incidence of septic death was similar among patients who received Herceptin and those
who did not.
- 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. Due to differences in tumor histopathology, use FDA-approved tests for the specific tumor
type (breast or gastric/gastroesophageal adenocarcinoma) to assess HER2 overexpression and HER2
gene amplification. Tests should be performed by laboratories with demonstrated proficiency in
the specific technology being utilized.
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.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may
also report side effects to Genentech at (888) 835-2555.
Please see the Herceptin full Prescribing Information including
Boxed WARNINGS and
additional important safety information.