Important Safety Information  |  Go to Patients & Caregivers Site ›

close

SAFETY

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
  • 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, in some cases complicated by pulmonary hypoplasia and neonatal death
  • Exacerbation of chemotherapy-induced neutropenia has also occurred
  • Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy
  • 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
Download the full Prescribing Information View full safety information ›

Safety First! Before you start exploring, take the time to read the Important Safety Information. Roll over to read more ›

  • FPO image

    Build a patient with HER2+ early-stage breast cancer and explore adjuvant treatment
    options based on trial results.
    Learn more ›

  • The importance of HER2 Testing

    It is important to share your HER2 test results with your care team. Learn more ›

Related Links & Downloads

In This Section:

Metastatic Breast Cancer Treatment Clinical Study Results

Herceptin in the first-line treatment of HER2+ metastatic breast cancer1

H0648g pivotal trial2

In a randomized, open-label clinical trial, a total of 469 patients with HER2+ metastatic breast cancer (defined as IHC 2+/3+) who had not received previous treatment for metastatic disease were randomized to receive Herceptin in combination with chemotherapy (CT) or CT alone.1

H0648g pivotal trial flowchart

AC=anthracycline (doxorubicin or epirubicin) with cyclophosphamide. Twenty patients in the Herceptin + AC arm and 16 in the AC alone arm received epirubicin rather than doxorubicin.

  • Primary endpoint: time to disease progression (TTP)2
  • Secondary endpoints: overall response rate (ORR), duration of response, and overall survival (OS)2
H0648g pivotal trial table
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.
  2. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-792.

Back to top

Herceptin is the only HER2-targeted monoclonal antibody with a proven survival benefit in HER2+ metastatic breast cancer, when combined with chemotherapy1

Herceptin + chemotherapy extended median OS in patients with HER2+ breast cancer1

Herceptin + chemotherapy extended median OS in patients with HER2+ breast cancer

AC=anthracycline (doxorubicin or epirubicin) with cyclophosphamide.
OS=overall survival.


  • Herceptin + CT increased median OS by 24% (P=0.046)1
    • Equated to 4.8 more months of life
  • 84% of patients in this trial had visceral metastases at enrollment2
  • 57.8% of all patients in this trial received prior hormonal therapy1

Boxed WARNING: Pulmonary Toxicity

  • 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
References
  1. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-792.
  2. Data on file. Genentech, Inc.

Back to top

Treatment with Herceptin plus chemotherapy provided a durable response1

Median TTP improved with Herceptin + chemotherapy

Median TTP improved with Herceptin + chemotherapy chart

AC=anthracycline (doxorubicin or epirubicin) with cyclophosphamide.
CT=paclitaxel or AC.
TTP=time to disease progression.

  • Herceptin + paclitaxel was associated with a median TTP of 6.7 months (95% CI: 5-10) vs 2.5 months (95% CI: 2-4) with paclitaxel alone (P=0.0001)1
  • Herceptin + AC was associated with a median TTP of 7.6 months (95% CI: 7-9) vs 5.7 months (95% CI: 5-7) with AC alone (P=0.002)1

Treatment with Herceptin + chemotherapy extended median duration of response1

Treatment with Herceptin + chemotherapy extended median duration of response chart

  • Herceptin + paclitaxel was associated with a median response duration of 8.3 months (25%, 75% quartile: 5, 11) vs 4.3 months (25%, 75% quartile: 4, 7) with paclitaxel alone1
  • Herceptin + AC was associated with a median response duration of 8.4 months (25%, 75% quartile: 6, 15) vs 6.4 months (25%, 75% quartile: 4, 8) with AC alone1

Boxed WARNING: 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 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 MotHER—the Herceptin Pregnancy Registry by calling 1-800-690-6720
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

Back to top

Treatment with Herceptin plus chemotherapy significantly improved response rate

Improved ORR in first-line metastatic breast cancer therapy1

Improved ORR in first-line metastatic breast cancer therapy chart

AC=anthracycline (doxorubicin or epirubicin) with cyclophosphamide.
CT=paclitaxel or AC.
ORR=overall response rate.

  • Herceptin + CT had up to 2.5 times the overall response of CT alone1
    • 50% response rate (95% CI: 42%-58%) with Herceptin + AC vs 38% (95% CI: 30%-46%) with AC alone (P=0.10)
    • 38% response rate (95% CI: 28%-48%) with Herceptin + paclitaxel vs 15% (95% CI: 8%-22%) with paclitaxel alone (P<0.001)

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
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

Back to top

Herceptin in the second- and third-line treatment of HER2+ metastatic breast cancer

H0649g pivotal trial1

Of 222 eligible patients with HER2+ (IHC 2+/3+) metastatic breast cancer that had progressed after receiving 1 or 2 prior chemotherapy regimens for metastatic disease, 213 were treated with Herceptin as a single agent in this open-label, single-arm clinical trial.1

H0649g pivotal trial

ORR=overall response rate
TTP=time to disease progression

  • Primary endpoint: objective response rate (ORR)1
  • Secondary endpoints: duration of response, time to disease progression (TTP), time to treatment failure, and survival1

Response to second- and third-line monotherapy2

  • In a heavily pretreated population of patients with a significant preexisting tumor burden:
    • 14% of intent-to-treat patients had a response2
      • 2% had a complete response, while 12% experienced a partial response
    • The overall response rate in patients whose tumors tested IHC 3+ was 18% compared with 6% in those tested as IHC 2+2

Boxed WARNING: Cardiac Monitoring

  • Evaluate cardiac function prior to and during treatment. For adjuvant 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
References
  1. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639-2648.
  2. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

Learn about Herceptin side effects in metastatic breast cancer ›

Indications

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 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

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

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

Cardiomyopathy

  • 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

Cardiac Monitoring

  • 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 treatment
  • Monitor more frequently if Herceptin is withheld for significant left ventricular cardiac dysfunction

Infusion Reactions

  • 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

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 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 MotHER—the Herceptin Pregnancy Registry by calling 1-800-690-6720

Pulmonary Toxicity

  • 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

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. 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

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

Herceptin

Herceptin