This site is for New Zealand healthcare professionals. If you are a patient, please click here.

Please enter your email address to view the content of this website.

Not a member? Register
You are here: Home / Our Medicines / Herceptin

Herceptin

Herceptin targets HER2 in early and metastatic breast cancer, as well as gastric cancer.

herceptin.jpg

Please review the Data Sheet before prescribing.

Herceptin is a humanised monoclonal antibody that specifically targets the HER2 receptor, which is overexpressed in certain cancers.1

There is a large evidence base to support Herceptin’s use in HER2-positive early and metastatic breast cancer.2-4

In addition, Herceptin has proven effective in advanced gastric cancer, as demonstrated in the ToGA trial.5

Herceptin is a Prescription Medicine, available as 150 mg single-dose vials and 440 mg multi-dose vials for intravenous (IV) infusion.1

For information on dosage and administration of Herceptin, please refer to the Data Sheet on the Medsafe website here.1

Herceptin’s Mechanism of Action

Herceptin specifically targets the HER2 receptor and has four distinct mechanisms of action:6

  • Activation of antibody-dependent cellular cytotoxicity (ADCC)
  • Prevention of the formation of p95-HER2, a truncated and very active form of HER2
  • Inhibition of cell proliferation by preventing HER2-activated intracellular signaling
  • Inhibition of HER2-regulated angiogenesis

Herceptin’s Funding Status

Herceptin is listed on the Pharmaceutical Schedule for the treatment of HER2-positive early and metastatic breast cancer.7 Refer to the Schedule for Special Authority information and forms.

Medsafe registered indications funded by PHARMAC:7

Metastatic breast cancer1

Herceptin is indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress HER2:

  • as monotherapy for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease; or
  • in combination with taxanes for the treatment of those patients who have not received chemotherapy for their metastatic disease; or
  • in combination with an aromatase inhibitor for the treatment of post-menopausal patients with hormone-receptor positive metastatic breast cancer.

Early breast cancer1

Herceptin is indicated for the treatment of patients with:

  • HER2-positive locally advanced breast cancer in combination with neoadjuvant chemotherapy, followed by adjuvant Herceptin; or
  • HER2-positive early breast cancer following surgery, sequentially or concurrently with chemotherapy and, if applicable, radiotherapy.

Medsafe registered indications not funded by PHARMAC:

Gastric cancer1

Herceptin is indicated in combination with cisplatin and either capecitabine or 5-FU for the treatment of patients with HER2- positive advanced adenocarcinoma of the stomach or gastro-oesophageal junction who have not received prior anti-cancer treatment for their metastatic disease.

Please refer to the Cost Share Programme section below for information on how we assist patients with the cost of Herceptin.

References

  1. Herceptin® (trastuzumab) Data Sheet. Available here
  2. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD006243. DOI: 10.1002/14651858.CD006243.pub2
  3. Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-1672.
  4. Marty M, Cognetti F, Maraninchi D et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer administered as first-line treatment: The M77001 Study Group. J Clin Oncol 2005; 23:4265-4274
  5. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-697.
  6. Hudis CA. Trastuzumab - mechanism of action and use in clinical practice. N Engl J Med 2007;357:39-51.
  7. PHARMAC Pharmaceutical Schedule. Available at http://www.pharmac.govt.nz/latest/SA1521.pdf Accessed 15 July 2016.

The Herceptin gastric Cost Share Programme (HgCSP) assists New Zealand patients with the cost of Herceptin for HER2-positive advanced gastric cancer. For more information on the program and criteria, click here. For an enrolment form click here.

Patients must be confirmed HER2 positive by:1

  • IHC3 positive, OR
  • IHC2 positive with confirmatory FISH positive test results from IGENZ (Roche funded service for HgAP patients)


If your patient has private health insurance, it may be worthwhile they check their policy regarding cancer treatments like Herceptin.

Health Insurance Quick Guide

For more information on the HgCSP, please contact us here.

Reference

1. Ruschoff J, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol 2012;25:637-50

Breast cancer

In the mid-1980s, preclinical evidence established the key role played by human epidermal growth factor receptor 2 (HER2) in normal breast cell growth and differentiation.1,2 Further research revealed that overexpression of HER2, usually as a result of HER2 gene amplification, occurs in approximately 20% of patients with breast cancer and is a negative prognostic marker.1-3 Women with HER2-positive breast cancer tend to have aggressive tumours, faster relapse times at all stages of cancer development and a poor overall prognosis.1-3

In the early breast cancer setting, four large randomised Phase III clinical trials [NSABP (B-31), NCCTG (N9831), HERA and BCIRG 006] showed significant reduction in disease recurrence with the addition of 52 weeks Herceptin to adjuvant chemotherapy, compared with chemotherapy alone.4-7

In the Phase III pivotal trial in patients with metastatic breast cancer, the addition of Herceptin to standard chemotherapy, increased median overall survival (OS) from 20.3 months to 25.1 months (p=0.046), compared with chemotherapy alone.8 Similarly in a Phase II study by Marty et al, the addition of Herceptin to docetaxel increased OS from 22.7 months to 31.2 months (p=0.0325), compared with docetaxel alone.9

Testing for HER2 breast cancer

IHC and FISH testing for HER2 status is fully funded by DHBs in New Zealand for early or metastatic breast cancer. If IHC results are <3, confirmatory FISH testing is required.

Advanced gastric cancer

Herceptin, when used in combination with chemotherapy, can extend survival in patients with HER2-positive advanced gastric cancer.10 In patients with IHC3+ or IHC2+/FISH+ HER2+ tumours, Herceptin improves median survival from 11.8 months to 16.0 months – a 4.2 month improvement over chemotherapy alone.10

Importantly, for patients with metastatic disease, treatment with Herceptin–plus-chemotherapy, maintained Quality of Life (QoL) compared to chemotherapy alone.11 Diarrhoea was the only side-effect with a higher grade 3/4 incidence than chemotherapy alone.10

Testing for HER2 in gastric cancer

It is important to note that HER2 testing in gastric cancer is different from breast cancer.12

HER2 status should be assessed via immunohistochemistry (IHC). If IHC results are <3, confirmatory FISH testing is required.12

IGENZ laboratory in Auckland are responsible for all confirmatory FISH testing for patients wishing to enrol in the Herceptin Gastric Cost Share Programme. We will fund this FISH testing.

Key Safety Information

For the full Herceptin safety information, please refer to the Data Sheet available here.13

Cardiac Dysfunction13

Congestive heart failure (CHF) or asymptomatic cardiac dysfunction (moderate to severe and has been associated with death); caution in patients with increased cardiac risk e.g. hypertension, documented coronary artery disease (CAD), CHF, diastolic dysfunction and older age; patients who receive anthracycline after stopping Herceptin may be at increased risk of cardiac dysfunction.

If possible avoid anthracycline-based therapy for up to 27 weeks after stopping Herceptin, if anthracyclines are used, the patient’s cardiac function should be monitored carefully. Perform baseline cardiac assessment with careful risk-benefit assessment before deciding to treat; monitor cardiac function every 3 months, or more frequently if asymptomatic cardiac dysfunction develops, continue monitoring every 6 months for 24 months after last dose of Herceptin dose.

Discontinue treatment if clinically significant heart failure develops, unless benefits outweigh risks.
Exercise caution in EBC patients with LVEF ≤ 55%, treatment not recommended if history of myocardial infarction, CHF, cardiac arrhythmias requiring medication, angina requiring medication, clinically significant valvular disease or poorly controlled hypertension.

Enhanced Safety Reporting for Potential Herceptin-Exposed Pregnancies

Please inform your patients about the potential risks related to the use of Herceptin in pregnancy and lactation and the need for effective contraception.

  • Herceptin should be avoided during pregnancy unless the potential benefit for the mother outweighs the potential risk to the foetus. There is a limited amount of data from the use of Herceptin in pregnant women, and the safe use of Herceptin during pregnancy and lactation has not been established.
  • In the post-marketing setting, cases of foetal renal growth and/or function impairment in association with oligohydramnios, some associated with fatal pulmonary hypoplasia of the foetus, have been reported in pregnant women receiving Herceptin.
  • Patients who become pregnant during Herceptin therapy or within 7 months following the last dose of Herceptin should be closely monitored for oligohydramnios.
  • It is not known whether Herceptin is secreted in human milk. As human IgG1 is secreted into human milk, and the potential for harm to the infant is unknown, women should not breastfeed during Herceptin therapy or for 7 months after the last dose.
  • There are no fertility data available.
  • Verify pregnancy status prior to the initiation of Herceptin. Womem of childbearing potential should use effective contraception while receiving Herceptin and for 7 months following the last dose of Herceptin.

If Herceptin is used during pregnancy or if a patient becomes pregnant while being treated with Herceptin or within 7 months following the last dose of Herceptin, immediately report the exposure to Roche on 0800 276 243 or email nz.drugsafety@roche.com.

Additional information will be requested during a Herceptin-exposed pregnancy and the first year of the infant’s life. This will enable Roche to better understand the safety of Herceptin and to provide appropriate information to health authorities, healthcare providers and patients.

Warnings and Precautions13

Hypersensitivity reactions including anaphylaxis

  • Severe hypersensitivity reactions reported infrequently. May occur during or after infusion. Some fatal.
  • Observe patients closely and interrupt treatment with severe reactions.

Signs/symptoms include anaphylaxis, urticarial, bronchospasm, angioedema and hypotension.

Infusion-related reactions (IRRs)

  • Pre-medication may be used to reduce risk of occurrence.
  • Some patients with acute onset of signs and symptoms initially improve followed by delayed reactions and rapid clinical deterioration. Fatalities have occurred within hours or up to one week following infusion.

Increased risk of fatal IRR in patients with dyspnoea at rest due to complications of advanced malignancy or comorbidities.

Observe patients closely. Interrupting infusion and treat symptoms appropriately.

Serious IRRs include dyspnoea, hypotension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation, respiratory distress and supraventricular tachyarrhythmia. Discontinue Herceptin in event of a severe IRR until symptoms resolved.

Pulmonary reactions

  • Reports of severe pulmonary events leading to death. May occur as part of IRR, hypersensitivity/anaphylaxis or with delayed onset.
  • Patients with dyspnoea at rest should not receive Herceptin.

Interstitial lung disease including lung infiltrates, acute respiratory distress syndrome, pneumonia, pneumonitis, pleural effusion, respiratory distress, acute pulmonary oedema and respiratory insufficiency reported.

Risks increased in patients with prior or concomitant therapy with taxanes, gemcitabine, vinorelbine and radiation therapy.

Cardiac dysfunction

  • Increased risk of CHF or asymptomatic cardiac dysfunction; can be moderate to severe and sometimes fatal.
  • Discontinue treatment if clinically significant CHF develops or LVEF does not improve, unless benefits outweigh risks.

Caution in patients with increased cardiac risk e.g. hypertension, coronary artery disease, CHF, diastolic dysfunction and older age.

Treatment not recommended if history of MI, CHF, cardiac arrhythmias or angina requiring medication, clinically significant valvular disease, poorly controlled hypertension and pericardial effusion.

Caution in EBC patients with age > 50 years, LVEF ≤ 55%, and prior antihypertensives

Anthracyline therapy increases risk of cardiac dysfunction. Do not give concurrently. If anthracycline given prior to Herceptin, perform baseline cardiac assessment and ongoing monitoring (see Data Sheet). If possible, avoid anthracycline-based therapy for up to 7 months post Herceptin.

Monitor cardiac function (see Data Sheet).

Pregnancy: Category D

  • Should be avoided during treatment and for 7 months after last dose (contraception advised)
  • Nursing mothers: avoid breast-feeding during treatment and for 7 months after last dose.

Undesirable Effects13

All indications (very common and common only; see Data Sheet for full list)

  • Infections/infestations: nasopharyngitis, infection, neutropenic sepsis, cystitis, herpes zoster, influenza, pharyngitis, sinusitis, skin infection, rhinitis, URTI, UTI, erysipelas, cellulitis.
  • Injury/poisoning: nail toxicity, contusion.

Blood/lymphatic: febrile neutropenia, anaemia, thrombocytopenia, leukopenia, neutropenia.

Immune system: Hypersensitivity.

Metabolism/nutrition: weight decrease/increase, decreased appetite, anorexia.

Psychiatric: insomnia, depression, anxiety, thinking abnormal.

Nervous system: tremor, dizziness, headache, dysgeusia, paraesthesia, hypoaesthesia, peripheral neuropathy, hypertonia, somnolence, ataxia.

Eye: conjunctivitis, increased lacrimation, dry eye.

Cardiac: blood pressure increase/decrease, irregular heartbeat, palpitation, cardiac flutter, decreased ejection fraction, cardiac failure, supraventricular tachyarrhythmia, cardiomyopathy.

Vascular: lymphoedema, hot flush, hypotension, hypertension, vasodilation.

Respiratory: wheezing, dyspnoea, cough, epistaxis, rhinorrhoea, oropharyngeal pain, asthma, lung disorder, pleural effusion, pneumonia.

GI: diarrhoea, vomiting, nausea, lip swelling, abdominal pain, stomatitis, constipation, dyspepsia, pancreatitis, haemorrhoids, dry mouth.

Hepatobiliary: Hepatocellular injury, hepatitis, liver tenderness.

Skin and SC: erythema, rash, face swelling, hand-foot syndrome, nail disorder, alopecia, dry skin, ecchymosis, hyperhidrosis, maculopapular rash, acne, onychoclasis, pruritus, dermatitis, urticaria.

Musculoskeletal: arthralgia, muscle tightness/spasms, myalgia, arthritis, neck, back, bone and extremity pain.

Renal/urinary: renal disorder.

Breast: breast inflammation/mastitis.

General/administration site disorders: asthenia, chest pain, chills, fatigue, influenza-like symptoms, IRR, pain, pyrexia, peripheral oedema, mucosal inflammation, malaise, oedema.

Please contact the Roche team for further information on the efficacy and/or safety of our products.

References

  1. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-182
  2. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707-712
  3. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med, 2007;131:18-43
  4. 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.
  5. Slamon D, Eiermann W, Robert N et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011;365:1273-83.
  6. Goldhirsch A, Gelber RD, Piccart Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 2013;382:1021–1028.
  7. Romond EH, Jeong J, Rastogi P. Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. J Clin Oncol 2012;30:3792-3799.
  8. 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;344:783-92.
  9. Marty M, Cognetti F, Maraninchi D et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer administered as first-line treatment: The M77001 Study Group. J Clin Oncol 2005; 23:4265-4274
  10. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-697.
  11. Satoh T, et al. Quality of life results from a phase III trial of trastuzumab plus chemotherapy in first-line HER2-positive advanced gastric and GE junction cancer. ASCO GI 2010. Oral Presentation #7
  12. Ruschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol 2012;25:637-50
  13. Herceptin® (trastuzumab) Data Sheet. Available here.

These booklets are a helpful source of information for patients. They are not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

More information for patients on Herceptin can be found at www.cancerinfo.co.nz and in the Consumer Medicine Information (CMI) leaflet, available here.

Click on the image to download the Herceptin eBC Booklet.

Herceptin eBC Booklet

Click on the image to download the Herceptin mBC Booklet.

Herceptin mBC Booklet

Click on the image to download the patient booklet ‘What does my pathology report mean?

Pathology Report data-verified=