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A - Regimen Name

KADC Regimen
Kadcyla® trastuzumab emtansine


Disease Site
Breast

Intent
Adjuvant

Regimen Category
Evidence-Informed :

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.


Rationale and Uses

For treatment of HER2+ patients with residual invasive disease at surgery after neoadjuvant therapy with a taxane and trastuzumab

 
B - Drug Regimen

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. 

Kadcyla® trastuzumab emtansine
3.6 mg /kg IV Day 1
(This drug is not currently publicly funded for this regimen and intent)
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

For a usual total of 14 cycles unless disease progression or unacceptable toxicity occurs

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal

Other Supportive Care:

Premedications for nausea and hypersensitivity have not been generally needed but may be given as necessary.
 
F - Adverse Effects

Refer to Kadcyla® trastuzumab emtansine drug monograph(s) for additional details of adverse effects


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • N/A
  • Nausea, vomiting
  • Fatigue
  • Musculoskeletal pain
  • Myelosuppression ± infection, bleeding (may be non-thrombocytopenic)
  • ↑ LFTs (may be severe)
  • Headache
  • Constipation
  • Diarrhea
  • Peripheral neuropathy (may be severe)
  • Abdominal pain
  • Cough, dyspnea
  • Dry mouth
  • Mucositis
  • Rash
  • Insomnia
  • Dizziness
  • Abnormal electrolytes (may be severe ↓K)
  • Cardiotoxicity
  • Hypersensitivity
  • Optic neuritis
  • Nodular regenerative hyperplasia and portal hypertension
  • Hepatic encephalopathy
  • Pneumonitis

 

 
G - Interactions

Refer to Kadcyla® trastuzumab emtansine drug monograph(s) for additional details


  • Avoid concomitant use with strong CYP3A4 inhibitors (e.g. azole antifungals, macrolide antibiotics). Consider delay of Kadcyla® trastuzumab emtansine treatment until CYP3A4 inhibitors have been cleared (about 3 elimination half-lives of the inhibitors). Monitor patient carefully if must co-administer.
  • Avoid concomitant use with anthracyclines and other cardiotoxic drugs; exercise extreme caution with anthracycline-based therapy for up to 24 weeks after stopping trastuzumab.
  • Exercise caution when used with anticoagulants (including antiplatelet agents); consider additional monitoring for bleeding if concurrent use is necessary
 
H - Drug Administration and Special Precautions

Refer to Kadcyla® trastuzumab emtansine drug monograph(s) for additional details


Kadcyla administration:

  • Reconstitute with sterile water for injection as directed and swirl gently.  Do not shake the solution.  Must be administered as an IV infusion.  Do not administer as an IV push or bolus.
  • Further dilute in 250 mL of 0.9% sodium chloride (NS) or 0.45% sodium chloride solutions only. 
  • Do not use dextrose 5% solution as this causes protein aggregation.
  • If diluted in NS, must use an in-line 0.2-micron in-line (non-protein absorptive) or 0.22-micron polyethersulfone (PES) filter for infusion.
  • Dilutions in 0.45% sodium chloride solution may be used without an in-line filter.
  • Administer the first infusion over 90 minutes, observe patient during the infusion and for at least 90 minutes after completion. 
  • If the first infusion is tolerated, may give subsequent infusions IV over 30 minutes; observe patient during the infusion and for at least 30 minutes after completion.
  • If the planned dose is missed, administer this as soon as possible.  Adjust the schedule to  maintain a 3-week interval between doses.
  • Also refer to Cancer Care Ontario's safety reminder for Kadcyla® Trastuzumab Emtansine.
  • Kadcyla® trastuzumab emtansine should not be admixed with other drugs. 
  • Store unopened vials in a refrigerator at 2-8oC.  Do not freeze.

Contraindications:

  • Patients who do not have HER2-overexpressed tumours (refer to dosing section)
  • Patients currently using trastuzumab (Herceptin®) or who had discontinued trastuzumab due to infusion reactions
  • Patients with baseline AST/ALT > 2.5 x ULN, bilirubin > 1.5 x ULN, grade 3 or 4 peripheral neuropathy, LVEF < 50%, or recent myocardial infarction/unstable angina within 6 months (Kadcyla has not been studied in these populations)

Other Warnings/Precautions:

  • Patients with dyspnea at rest due to complications of advanced cancer and co-morbidities may be at increased risk of pulmonary events.
  • Patients with previous history or at risk of neuropathy (e.g. previous neurotoxic drugs)
  • The risk of cardiotoxicity must be weighed against the potential benefits of treatment, especially in older patients, patients with pre-existing cardiac disease (including LVEF 50-55%) and patients who have had prior cardiotoxic therapy.
 
I - Recommended Clinical Monitoring

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

  • CBC; baseline and before each dose and as clinically indicated
  • Liver function tests; baseline and before each dose, more frequent in patients who have severe LFT increases
  • LVEF (echocardiogram or MUGA scan); baseline and q3 months during treatment, more frequent with asymptomatic reductions in LVEF; also suggest q6 months after treatment discontinuation x2 years, and as clinically indicated
  • Clinical toxicity assessment for infection, bleeding, musculoskeletal pain, fatigue, rash, hypersensitivity or infusion reactions, neurotoxicity, GI and pulmonary effects; at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
First cycle: 1.5-2 hours; Subsequent cycles: 0.5-1 hour
Pharmacy Workload (average time per visit)
19.589 minutes
Nursing Workload (average time per visit)
49.722 minutes
 
K - References

von Minckwitz G et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380:617-28.

Kadcyla drug monograph, Cancer Care Ontario.

April 2019 New ST-QBP regimen


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M - Disclaimer

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.