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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
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In This Section:

Adjuvant Breast Cancer Treatment Clinical Study Results

One year of Herceptin plus standard adjuvant therapy significantly reduced the risk of disease recurrence1-4

Four pivotal trials involving more than 10,000 women demonstrated that 1 year of Herceptin therapy provided significant clinical benefit1-4

Herceptin therapy clinical benefit

AC=anthracycline (doxorubicin) plus cyclophosphamide.
T=Taxotere® (docetaxel) (in BCIRG 006) or paclitaxel (in the Joint Analysis).
C=carboplatin (in the TCH regimen).
H=Herceptin.
*Recurrence was defined as any clinical or radiologic evidence of tumor recurrence.
†Patients were randomized upon completion of chemotherapy, surgery, and radiotherapy (if appropriate).
Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

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. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673-1684 and supplementary appendix.
  2. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.
  3. Data on file. Genentech, Inc.
  4. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.

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BCIRG 006

BCIRG 006 Herceptin adjuvant breast cancer trial

AC=anthracycline (doxorubicin) plus cyclophosphamide.
T=Taxotere® (docetaxel) (in BCIRG 006) or paclitaxel (in the Joint Analysis).
C=carboplatin (in the TCH regimen).
H=Herceptin.
Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

  • This phase 3 trial evaluated the efficacy and safety of adding Herceptin to both an anthracycline-based and a non-anthracycline-containing adjuvant chemotherapy regimen1
    • Study was designed to compare results from each of the Herceptin-containing arms with those from the control arm—not with each other
  • Patients [N=3222] were randomized (1:1:1) to receive 1 of the following regimens:1
    • TCH: Taxotere and carboplatin plus Herceptin
    • AC→TH: doxorubicin and cyclophosphamide followed by Taxotere plus Herceptin
    • AC→T (control): doxorubicin and cyclophosphamide followed by Taxotere
  • 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
  • This clinical trial, conducted by the Breast Cancer International Research Group (BCIRG), evaluated efficacy and cardiac safety of 2 Herceptin-containing regimens vs a control (N=3222)

Boxed WARNING: 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
  • 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
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

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BCIRG 006 demonstrated that 1 year of Herceptin improved disease-free survival (DFS) with either TCH or AC→TH regimens1

TCH (a non-anthracycline regimen) provided a significant reduction in the risk of disease recurrence that was consistent with AC→TH (an anthracycline-containing regimen)1

BCIRG 006 Herceptin adjuvant breast cancer trial results

AC=anthracycline (doxorubicin) plus cyclophosphamide.
T=Taxotere® (docetaxel) (in BCIRG 006) or paclitaxel (in the Joint Analysis).
C=carboplatin (in the TCH regimen).
H=Herceptin.
Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

  • At 3 years, absolute risk of disease recurrence was decreased by:
    • 4.0% in the TCH arm compared with AC→T (95% CI: 0.6%-7.4%)2
    • 5.7% in the AC→TH arm compared with AC→T (95% CI: 2.4%-9.0%)2
  • TCH regimen offers earlier initiation of Herceptin and shorter duration of infused therapy compared with AC→TH
    • The TCH regimen enables immediate initiation of Herceptin with chemotherapy
      • This differs from AC→TH, in which Herceptin is started only after 12 weeks of AC have been completed
    • The TCH regimen reduces the overall duration of infused therapy to 12 months total, since all chemotherapies are given concurrently with Herceptin
      • Since Herceptin should not be administered concurrently with AC, the sequential order of AC→TH extends infused therapy to 15 months total
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.
  2. Data on file. Genentech, Inc.

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HERA (HERceptin Adjuvant trial)

HERA (HERceptin adjuvant breast cancer trial)

  • This international multicenter, randomized, open-label, multi-modality controlled clinical trial conducted by the Breast International Group (BIG) evaluated the effect of Herceptin monotherapy after initial therapy in the adjuvant treatment of HER2+ breast cancer1
  • Within 6 months of completing surgery, anthracycline-based chemotherapy, and radiation therapy (if indicated), patients were either assigned to an observation group or given Herceptin every 3 weeks for 1 year or 2 years* (N=3386)1
  • Hormonal therapy was administered concurrently with Herceptin to patients with ER+ and/or PR+ breast cancer (as appropriate)1
  • The primary endpoint was disease-free survival (DFS)

*Data from the 2-year arm are not yet reported.

Boxed WARNING: 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 anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.

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HERA supported the DFS benefit provided by 1 year of Herceptin1

Herceptin reduced the risk of disease recurrence by 46%2

HERA (HERceptin adjuvant breast cancer trial) results

  • At 2 years, absolute risk of disease recurrence was decreased by 7.6% in the 1-year Herceptin arm of the study compared with the observation arm3
  • The risk of distant disease recurrence* was reduced by more than half

*Distant disease recurrence was defined as time from randomization to the development of tumor in any nonlocal/nonregional site.

References
  1. Herceptin Prescribing Information. Genentech, Inc. October 29, 2010.
  2. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.N Engl J Med. 2005;353:1659-1672.
  3. Data on file. Genentech, Inc.

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Joint Analysis of NSABP B-31 and NCCTG N9831

Joint analysis of NSABP B-31 and NCCTG N9831 adjuvant breast cancer trials

*In NCCTG N9831, there was a sequential third arm that was not analyzed as part of the Joint Analysis.
AC=anthracycline (doxorubicin) plus cyclophosphamide.
T=Taxotere® (docetaxel) (in BCIRG 006) or paclitaxel (in the Joint Analysis).
C=carboplatin (in the TCH regimen).
H=Herceptin.
Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

  • 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 regimens:1
    • 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 appropriate2

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.
  2. Data on file. Genentech, Inc.

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Joint Analysis showed that 1 year of Herceptin significantly improved DFS1

Herceptin plus chemotherapy reduced the risk of disease recurrence
by 52%1

Joint Analysis of NSABP B-31 and NCCTG N9831 adjuvant breast cancer trials results

AC=anthracycline (doxorubicin) plus cyclophosphamide.
T=Taxotere® (docetaxel) (in BCIRG 006) or paclitaxel (in the Joint Analysis).
C=carboplatin (in the TCH regimen).
H=Herceptin.
Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

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

Learn more about Herceptin side effects in clinical trials in adjuvant 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