Pivotal Studies and Efficacy Data

The only HER2-targeted agent with proven survival benefit in HER2+ metastatic breast cancer

Extended median survival

  • Herceptin (trastuzumab) is the only HER2-targeted agent to demonstrate a survival advantage when added to chemotherapy, in the first-line treatment of metastatic breast cancer 1,2
Graph: Median survival benefits observed with HER2 gene amplification

Study design: 469 patients with HER2+ metastatic breast cancer who had not received previous treatment for metastatic disease were randomized to receive either standard chemotherapy alone or standard chemotherapy plus Herceptin.

  • Adding Herceptin to chemotherapy increased median survival by 24%
  • Equated to 4.8 more months of life
  • 84% of patients studied had visceral metastases at enrollment 4
  • Trial included a high-risk patient population

Metastatic 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

Boxed WARNINGS and Additional Important Safety Information1

Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection failure. 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 for breast cancer and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.

73%-79% of patients alive at one year 4

Graph: Improved 1-year survival

*Chemotherapy was either doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel.

Sustained clinical benefit in the first-line combination treatment of HER2+ metastatic breast cancer.

More months without disease progression 1

Patients receiving AC or paclitaxel*

  • Among all patients, regardless of the chemotherapy regimen used,*adding Herceptin improved median time to progression1
Graph: Median time to progression

*Chemotherapy was either doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel.

  • First-line Herceptin was administered during chemotherapy and continued until disease progression 2
  • Chemotherapy was administered for an average of six cycles
  • A median of 36 doses of Herceptin was given (range: 1 to 98)
  • Patients receiving paclitaxel1
  • Among the subset of patients receiving paclitaxel, adding Herceptin more than doubled median time to progression (P<0.0001)
    • 6.7 months for patients receiving Herceptin plus paclitaxel
    • 2.5 months for patients receiving paclitaxel alone

Durable response

  • Patients receiving AC or paclitaxel*
  • Among all patients, regardless of the chemotherapy regimen used, Herceptin plus chemotherapy prolonged clinical benefits versus chemotherapy alone*
Graph: Progression-free survival

*Chemotherapy was either doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel.

  • Patients receiving paclitaxel
  • Among the subset of patients receiving paclitaxel and Herceptin 4:
    • 41% were surviving progression-free at eight months (P<0.0001 vs paclitaxel alone)
    • 26% were surviving progression-free at 12 months
  • There were insufficient data to determine the percentage of patients who were progression-free at 18 months

Boxed WARNINGS and Additional Important Safety Information1

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.

In the treatment of HER2+ metastatic breast cancer, Herceptin has a demonstrated response in first-line, second-line, and third-line therapy.

Response to first-line combination use

Benefits of Herceptin were observed regardless of age, ER/PR status, overall tumor burden, or location of metastases 4

  • Herceptin resulted in up to 2.5 times the overall response of chemotherapy alone 1
    • 38% response rate (Herceptin + paclitaxel) vs 15% for paclitaxel alone (P<0.001)
    • 45% response rate (Herceptin + chemotherapy) vs 29% for chemotherapy alone (P<0.001)
Graph: Overall response rate

*Chemotherapy was either doxorubicin or epirubicin plus cyclophosphamide, or paclitaxel.

Response to second-line or third-line monotherapy

  • In a heavily pretreated population of patients with significant pre-existing tumor burdens:
  • 20% response rate among patients with tumors testing FISH+ (based on a retrospective analysis) 1,4
  • 15% response rate among patients with tumors testing IHC 2+ or 3+ 1,5

Well-established safety profile

More than 10 years of clinical use consistently report the most serious and most common adverse events associated with Herceptin1

Cardiac safety profile

Incidence and severity of cardiac dysfunction

In clinical trials in the metastatic setting, most patients with cardiac dysfunction responded to appropriate medical therapy, often including discontinuation of Herceptin2

  • Adjuvant 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 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

Boxed WARNINGS and Additional Important Safety Information

  • Cardiotoxicity
  • 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 for breast cancer and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.
  • Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death.
    • In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.
    • Herceptin can also cause asymptomatic decline in LVEF.
  • Cardiac Monitoring
  • Candidates for treatment with Herceptin should undergo a thorough baseline cardiac assessment, including history, physical examination, and an assessment of LVEF by echocardiogram or MUGA scan.
    • Patients should undergo frequent monitoring for decreased left ventricular function during and after Herceptin treatment.
    • More frequent monitoring should be employed if Herceptin is withheld in patients who develop significant left ventricular cardiac dysfunction.
  • Infusion reactions and Pulmonary Toxicity
  • 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
  • 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.
    • In postmarketing reports, serious and fatal infusion reactions have been reported. Discontinue Herceptin in all patients with severe or life-threatening infusion reactions.
  • Herceptin use 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.
  • Neutropenia
  • Exacerbation of chemotherapy-induced neutropenia has also occurred
    • In controlled clinical trials, severe neutropenia and febrile neutropenia occurred more frequently in metastatic breast cancer patients receiving Herceptin with myelosuppressive chemotherapy compared to chemotherapy alone.
    • The incidence of septic death was not significantly increased.
  • Pregnancy Category D
  • Herceptin can cause fetal harm when administered to a pregnant woman.
  • Post-marketing reports suggest that Herceptin use during pregnancy increases the risk of oligohydramnios during the second and third trimester.
  • 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. 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. NEngl J Med.2001; 344: 783-792.
  • 3. Mass RD, Press M, Anderson S, et al. Improved survival benefit from Herceptin (trastuzumab) in patients selected by fluorescence in situ hybridization (FISH) [abstract]. Proc Am Soc Clin Oncol. 2001; 20: 22a. Abstract 85 and Presentation.
  • 4. Data on file. Genentech, Inc.
  • 5. Cobleigh MA, Vogel CL, Tripathy D, etal. 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. JClin Oncol.1999; 17: 2639-2648.


Herceptin® (trastuzumab)Herceptin® (trastuzumab)