The BCIRG 006 trial

Study Design1

  • This clinical trail, conducted by the Breast Cancer International Research Group (BCIRG), evaluated the efficacy and safety of 2 Herceptin-containing regimens vs a control (n=3222).
  • Patients were randomized (1:1:1) to receive one of the following adjuvant regimens:
    • TCH: Taxotere®* (docetaxel) 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 and/or radiotherapy were given as appropriate.
Diagram: BCIRG 006 Study Design

Taxotere® and carboplatin plus Herceptin (TCH) demonstrated efficacy in BCIRG 006

TCH (Taxotere and carboplatin plus Herceptin) regimen provided benefit consistent with AC→TH1

Diagram: BCIRG 006 Disease Free Survival
  • The risk of disease recurrence was significantly reduced with TCH compared with AC→T1.
  • At 3 years, there was an absolute reduction in the risk of disease recurrence of 4.0% in the TCH arm (95% confidence interval: 0.6%-7.4%), compared with AC→T2.

Boxed WARNINGS and Additional Important Safety Information

Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction. Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported. Exacerbation of chemotherapy-induced neutropenia has also occurred. 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.

TCH demonstrated consistent benefit across patient subgroups

TCH (Taxotere and carboplatin plus Herceptin) regimen improved DFS across diverse subgroups2.

Chart: DFS by subgroup

29% of patients enrolled had high-risk† node-negative disease

Results within patient subgroups were generally consistent with the overall treatment effects

  • Exploratory analyses for the risk of recurrence, contralateral breast cancer, or death within patient subgroups were generally consistent with the overall treatment effects

There were insufficient numbers of patients within each of the following subgroups to determine if the treatment effect for them was different from that for the overall patient population1

  • Patients with low tumor grade
  • Patients within specific ethnic/racial subgroups (Black, Hispanic,Asian/Pacific Islander)
  • Patients >65 years of age

TCH regimen offers earlier initiation and shorter duration than AC→TH1

  • 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

† High-risk features were defined as: tumor that was ER-negative and PR-negative, tumor size >2 cm, histologic and/or nuclear grade 2/3, and age <35 years.

AC→TH lowered risk of recurrence in BCIRG 006

AC→TH reduced risk of recurrence vs AC→T1

Chart: DFS by subgroup
  • The risk of recurrence was significantly reduced with AC→TH compared with AC→T1.
  • At 3 years, there was an absolute reduction in the risk of disease recurrence of 5.7% in the AC→TH arm (95% confidence interval: 2.4%-9.0%) compared with AC→T2.

AC→TH demonstrated consistent benefit across patient subgroups

AC→TH regimen improved DFS across diverse subgroups2

Chart: DFS by subgroup

29% of patients enrolled had high-risk‡ node-negative disease

Results within patient subgroups were generally consistent with the overall treatment effects

  • Exploratory analyses for the risk of recurrence, contralateral breast cancer, or death within patient subgroups were generally consistent with the overall treatment effects

There were insufficient numbers of patients within each of the following subgroups to determine if the treatment effect for them was different from that for the overall patient population1

  • Patients with low tumor grade
  • Patients within specific ethnic/racial subgroups (Black, Hispanic,Asian/Pacific Islander)
  • Patients >65 years of age

‡ High-risk features were defined as: tumor that was ER-negative and PR-negative, tumor size >2 cm, histologic and/or nuclear grade 2/3, and age <35 years.

Boxed WARNINGS and Additional Important Safety Information

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 and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function. In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.

Improving completion rates of planned Herceptin treatment with TCH

Lower risk of cardiac-related discontinuation

  • The TCH regimen (Taxotere and carboplatin plus Herceptin) eliminates the potential for anthracycline-related cardiotoxicity that may prevent Herceptin initiation.
  • 2.9% of patients in the TCH arm discontinued Herceptin due to a cardiac event compared with 5.7% of patients in the AC→TH arm1.

Higher completion rates2

On average, for every 100 patients receiving a Herceptin-containing regimen in BCIRG 006, 13 more were able to complete therapy with TCH.

Chart: Patients unable to complete planned adjuvant therapy

    In the AC→TH arm, 2.3% of patients in the safety population* discontinued therapy prior to receiving any Herceptin.

    • Herceptin was initiated in 100% of patients in the safety population for the TCH arm

    91.3% of patients in the AC→TH arm and 95.5% of patients in the TCH arm started Herceptin monotherapy after completion of chemotherapy.

    • Herceptin was discontinued during monotherapy in 10% of patients in the AC→TH arm and 5.4% of patients in the TCH arm

    * Includes all patients who recieved at least 1 dose of study treatments.

    Table: Incidence of CHF

    Reducing cardiac risk with TCH

    Reduced cardiac risk in non-anthracycline regimen1

    • In BCIRG 006, a lower rate of congestive heart failure (CHF) was seen with the TCH regimen (Taxotere and carboplatin plus Herceptin) vs the AC→TH regimen
    Table: Incidence of CHF
    • Patients were ineligible if they had a history of CHF, myocardial infarction, grade 3 or 4 cardiac arrhythmia, angina requiring medication, clinically significant valvular heart disease, poorly controlled hypertension (diastolic >100 mm Hg), any T4 or N2 or known N3 or M1 breast cancer.
    • The incidence of NCI-CTC grade 3/4 cardiac ischemia/infarction was higher in the Herceptin-containing regimens as compared with AC→T.
      • 0.3% (3/1068) with AC→TH; 0.2% (2/1056) with TCH; and 0% with AC→T

    Reduced risk of asymptomatic LVEF drops in non-anthracycline regimen1

    Table: Per-patient incidence of new-onset cardiace dysfunction

    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
    • 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.



Herceptin® (trastuzumab)Herceptin® (trastuzumab)