Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
TRAS
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
- Single agent or combination treatment of HER2 positive metastatic breast cancer in patients who have not had trastuzumab in the metastatic setting (refer to NDFP form for details)
- For retreatment of HER2 positive metastatic breast cancer when used in combination with chemotherapy (but not lapatinib), after previous exposure to trastuzumab-based treatments in the metastatic setting. Trastuzumab is not eligible for NDFP funding if the patient has progressed on lapatinib for the 2nd-line treatment of HER2 positive metastatic breast cancer
Note: A patient whose disease has progressed from first line trastuzumab and second line Kadcyla® trastuzumab emtansine will not be eligible for funding of third line “lapatinib-capecitabine”.
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) - Single Agent - Metastatic Breast Cancer)
(PDRP (NDFP) funding is contingent on the patient previously receiving chemotherapy.
)
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) - Second Line - Metastatic Breast Cancer)
(PDRP (NDFP) funding is contingent on the patient previously receiving chemotherapy.
)
Note: Different trastuzumab products are NOT INTERCHANGEABLE.
Loading dose (cycle 1):
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trastuzumab 1, 2 | 8 mg /kg | IV over 90 minutes | Day 1 |
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Maintenance dose (starting cycle 2):
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trastuzumab 1, 2 | 6 mg /kg | IV over 30 minutes* | Day 1 |
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*If loading dose was well-tolerated 1May be administered sequentially (all chemotherapy regimens) or concurrently (non-anthracycline containing regimens only). 2In general, the dose of trastuzumab should be delayed if the chemotherapy cycle is delayed for scheduling convenience. |
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Minimal
Low
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Dosage with Myelosuppression: No adjustment required
Dosage with Cardiotoxicity:
Product Monograph recommendations
- Trastuzumab should be held with a fall in LVEF (product monograph suggests if LVEF falls ≥10 points from baseline and/or if LVEF falls to < 50%). Repeat LVEF in 3 weeks and consider discontinuing. Discontinue if clinically significant cardiac dysfunction or cardiac failure develops.
Canadian Consensus Guidelines
- Discontinue if symptomatic.
Management of trastuzumab therapy in adjuvant breast cancer patients with asymptomatic decreases in LVEF (Mackey et al 2008):
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Relationship of LVEF to Lower Limit of Normal (LLN) |
Trastuzumab dose modification based on asymptomatic LVEF decrease from baseline |
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≤ 10 percentage points |
10-15 percentage points |
≥ 15 percentage points |
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Within facility’s normal limits |
Continue |
Continue |
Hold and repeat MUGA/ECHO after 4 weeks |
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1-5% below LLN |
Continue 1 |
Hold and repeat MUGA/ECHO after 4 weeks 1, 2 |
Hold and repeat MUGA/ECHO after 4 weeks 2, 3 |
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≥ 6% below LLN |
Continue and repeat MUGA/ECHO after 4 weeks 3 |
Hold and repeat MUGA/ECHO after 4 weeks 2, 3 |
Hold and repeat MUGA/ECHO after 4 weeks 2,3 |
1 Consider cardiac assessment and starting ACEI therapy
2 After 2 holds, consider permanent trastuzumab discontinuation
3 Start ACEI therapy and refer to cardiologist
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
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| 3 or 4 |
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Dosage with other toxicity:
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Toxicity |
Action | ||
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Pulmonary Toxicity |
Discontinue permanently and manage symptoms aggressively with beta-agonists, antihistamines and/or corticosteroids. Do not re-challenge. |
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Hepatic Impairment
No adjustment required.
Renal Impairment
No adjustment required. The disposition of trastuzumab is not altered based on serum creatinine.
Dosage in the Elderly
No adjustment required; the risk of cardiac dysfunction and myelosuppression may be increased in elderly patients. The reported trials did not determine differences in efficacy between patients ≥ 65 years versus younger patients.
Refer to trastuzumab drug monograph(s) for additional details of adverse effects
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Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to trastuzumab drug monograph(s) for additional details
- Avoid concomitant use with anthracyclines and other cardiotoxic drugs. Use with extreme caution with anthracyclines for up to 28 weeks after stopping trastuzumab.
Refer to trastuzumab drug monograph(s) for additional details
Note: Different trastuzumab products are NOT INTERCHANGEABLE.
Administration
NOTE: Herceptin® (trastuzumab) and Kadcyla® (trastuzumab emtansine) are NON-INTERCHANAGEABLE. There have been fatal reports where the incorrect trastuzumab product was administered to patients with breast cancer in the clinical trials setting.
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DO NOT ADMINISTER AS AN IV PUSH OR BOLUS.
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Mix in 250 mL bag NS. Do not use D5W as it causes protein aggregation. Do not shake.
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Administer loading dose over 90 minutes. Observe during the infusion and for at least 90 minutes after the infusion.
- If no previous IR, subsequent infusions may be administered over 30 minutes. Observe patients during the infusions and for at least 30 minutes after the infusions.
- Should not be mixed or diluted with other drugs.
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Compatible with polyvinylchloride, polyethylene or polypropylene bags
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Diluent supplied - Bacteriostatic Water for Injection (BWFI) - contains benzyl alcohol 1.1%; if patient is hypersensitive to benzyl alcohol, may reconstitute with Sterile Water for Injection, but must be used immediately and discard unused portion.
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Solution reconstituted with the supplied BWFI is stable up to 28 days refrigerated.
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Do not freeze the reconstituted solution.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
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Patients with known hypersensitivity to trastuzumab, Chinese Hamster Ovary (CHO) cell proteins, or any components of this product.
Other Warnings/Precautions
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Trastuzumab should only be used in patients whose tumours overexpress HER2. Refer to product monograph for details on testing.
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The risk of cardiotoxicity must be weighed against the potential benefits of treatment, especially in older patients and patients who have had prior cardiotoxic therapy. Use extreme caution in patients with pre-existing cardiac dysfunction (including LVEF < 55% in early breast cancer). Note: in the adjuvant trials, patients with cardiac risk factors were excluded from the trials.
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Exercise caution in patients with pre-existing pulmonary disease, patients with extensive pulmonary tumour involvement or patients with previous chemo or radiation therapies known to be associated with pulmonary toxicities, as they may experience more severe lung toxicities.
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Patients with dyspnea at rest due to advanced malignancy complications and comorbidities should not treated with trastuzumab, as they may be at increased risk of a fatal infusion reaction or pulmonary events.
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Consider appropriate management of patients with uncontrolled hypertension or history of hypertension before starting trastuzumab.
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Use with caution before or after anthracyclines (for up to 28 weeks after trastuzumab discontinuation due to long half-life).
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Life-threatening infusion-related reactions associated with the administration of trastuzumab may occur.
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Benzyl alcohol (a preservative in BWFI) has been associated with toxicity in neonates and children up to 3 years old.
Pregnancy / Lactation
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Trastuzumab is not recommended for use in pregnancy. Impairment of fetal renal growth and/or function impairment resulting in oligohydramnios (including neonatal fatal cases) have been reported. Adequate contraception should be used by both sexes during treatment, and for at least 7 months after the last dose. Monitor for oligohydramnios in patients who become pregnant during trastuzumab therapy. Perform appropriate fetal testing if oligohydramnios occurs.
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Breastfeeding is not recommended.
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Fertility effects: Unknown.
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No data in humans; animal studies showed no evidence of impaired fertility.
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Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
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Infusion-associated symptoms; During the infusion and observe for at least 90 minutes afterwards (for loading dose), and at least 30 minutes afterwards (maintenance dose)
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Cardiac assessment, including evaluation of left ventricular function (Echocardiogram or MUGA scan); Baseline, q3 months during treatment, then q6 months after trastuzumab discontinuation x2 years (and annually up to 5 years after last trastuzumab dose in adjuvant breast cancer patients who received anthracyclines), or longer if continued LVEF decrease, also as clinically indicated (more frequent monitoring in asymptomatic LVEF reductions)
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Clinical exam for symptoms of cardiac failure, pulmonary toxicity and diarrhea; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
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CBC; As clinically indicated
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Liver function tests; As clinically indicated
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Andersson M, Lidbrink E, Bjerre K, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol 2011;29(3):264-71.
Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366(2):109-19.
Burstein HJ, Keshaviah A, Baron AD, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer 2007;110(5):965-72.
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.
de Lemos ML, Mason K, Badry N, et al. Trastuzumab therapy in breast cancer: To reload or not to reload? J Oncol Pharm Pract 2014 Aug;20(4):319-20.
Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol. 2003 Nov 1; 21(21):3965-71.
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(11):783-92.
Trastuzumab drug monograph, Cancer Care Ontario.
Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of Treatment of Metastatic Breast Cancer With Trastuzumab Beyond Disease Progression. J Clin Oncol 2004; 22: 1063-70.
von Minckwitz G, Schwedler K, Schmidt M, et al. Trastuzumab beyond progression: Overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer 2011; 47: 2273-81.
October 2023 Updated the "Rationale and Uses" section
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.