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You are here: Home / Our Medicines / Kadcyla

Kadcyla

Kadcyla is an antibody-drug conjugate for HER2-positive metastatic breast cancer.

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Please review the Data Sheet before prescribing.

Kadcyla is the first antibody-drug conjugate (ADC) for HER2-positive metastatic breast cancer (mBC), combining the chemotherapy DM1 and Herceptin® (trastuzumab) together in a single treatment. 1-2

Medsafe-registered indications¹

Kadcyla, as a single agent, is indicated for the treatment of patients with HER2-positive metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:

  • Received prior therapy for metastatic disease, or
  • Developed disease recurrence during, or within six months of completing adjuvant therapy.

Kadcyla is a Prescription Medicine, available as 100mg and 160mg single-use vials for intravenous (IV) infusion.

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

Kadcyla’s Mechanism of Action

Kadcyla combines the monoclonal antibody Herceptin with the small molecule cytotoxic DM1 to deliver a targeted antibody-drug conjugate, which retains the mechanisms of action of both components. 1-3

Herceptin specifically targets the HER2 receptor and has four distinct mechanisms of action:4

  • 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

The process by which Kadcyla acts on cancer cells is:3

  1. Kadcyla selectively binds to the HER2 receptor at subdomain IV
  2. Once bound, the Kadcyla/HER2 receptor complex is internalised via endocytosis
  3. Kadcyla is degraded inside the cell to release DM1
  4. DM1 binds to microtubules and inhibits their polymerization, causing cell-cycle arrest and cell death

For a short video explaining Kadcyla’s mode of action, click on the image below.

Kadcyla’s funding status

Kadcyla is not funded by PHARMAC and patients need to pay for it.

We provide a Cost Share Programme to assist with the cost of Kadcyla for previously-treated HER2 positive metastatic breast cancer.

For patients who have progressed on Perjeta ® (pertuzumab) and are eligible for Kadcyla as second line treatment, we also provide a Bridging Cost Share Programme. Please refer to the Cost Share Programme section below for more information.

References:

  1. Kadcyla® (trastuzumab emtansine) Data Sheet. Available here.
  2. Junttila TT, Li G, Parsons K et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128(2):347-356.
  3. Erickson HK, Park PU, Widdison WC et al. Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 2006;66:4426-4433
  4. Hudis CA. Trastuzumab - mechanism of action and use in clinical practice. N Engl J Med 2007;357:39-51.


The Kadcyla Cost Share Programme assists with the cost of Kadcyla for New Zealand patients with previously treated HER2-positive metastatic breast cancer (mBC).

The Kadcyla Cost Share Programme criteria are:

  1. Patient has received previous Herceptin® (trastuzumab) for first line, HER2-positive mBC and has disease progression*^
    Or
  2. Patient has progressed within 6 months of adjuvant Herceptin treatment for early breast cancer*^

* Roche reserves the right to request information to confirm the eligibility of the patient for the cost share programme and may from time to time request an update on the patient's condition.

^ where information is reported which constitutes disease progression this will be provided to Roche Drug Safety who may also request additional information.

Bridging Cost Share Programme from Perjeta® (pertuzumab) to Kadcyla

For patients who have progressed on Perjeta and are eligible for Kadcyla as second line treatment, we also provide a Bridging Cost Share Programme.

Patients who have paid for Perjeta treatment may access Kadcyla at a reduced cost. The aim of the Bridging Programme is to cap the cost of treatment and provide access for patients with HER2-positive mBC to both Perjeta and Kadcyla.

The Bridging Programme eligibility criteria are:

  1. A patient must have been enrolled in the Perjeta Cost Share Programme.
  2. The patient must have experienced disease progression on Perjeta + Herceptin or stopped treatment due to toxicity.

Roche may require supporting evidence to confirm patient eligibility. Enrolment must occur prior to patients receiving free treatment.

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

Health Insurance Quick Guide

All the details of the Kadcyla Cost Share Programme and the Bridging Programme are in the ‘HER2-positive Metastatic Breast Cancer (mBC) Cost Share Programmes’ brochure. Click on the image to download a copy.

HER2-positive mBC Cost Share Programmes Brochure

Click on the images to download copies of the Cost Share Programme enrolment form and claim form.

KadcylaCSP_EnrolmentForm

Kadcyla Cost Share Programme Enrolment Form

Kadcyla Cost Share Programme Claim Form

Treatment of mBC is about stopping or slowing the progression of disease.1 This usually involves a number of treatments over time.1 HER2-positive mBC has in the past been associated with poor clinical outcomes.2 However, newer treatments have improved the survival of patients with this disease.3,4

In the EMILIA trial, Kadcyla extended median progression free survival by 3.2 months, compared to lapatinib plus capecitabine. More than 35% of patients were still receiving treatment with Kadcyla at 12 months, with approximately 20% still on treatment at 2 years.5

EMILIA study

A randomized, international, multicentre, 2-arm, open-label, Phase III study was conducted to evaluate the safety and efficacy of Kadcyla (n=495) compared with lapatinib plus capecitabine (n=496) in patients with locally advanced or mBC. Eligible patients had previously received both a taxane and trastuzumab, but progressed during or after the most recent treatment for mBC, or within 6 months of adjuvant treatment.

Progression free survival (PFS)

After a median duration of follow-up of 13 months, the study met its primary endpoint by showing an improvement in PFS in patients who received Kadcyla (HR=0.65; 95% CI, 0.55-0.77; p<0.001). Median PFS was 9.6 months in the Kadcyla arm and 6.4 months in the lapatinib plus capecitabine arm.

Overall Survival (OS)

At the second interim OS analysis, after a median follow-up of 19 months, Kadcyla significantly improved OS compared to lapatinib plus capecitabine (HR=0.68; 95% CI, 0.55-0.85; p<0.0001). The median OS was 30.9 months in the Kadcyla arm compared to 25.1 months in the lapatinib plus capecitabine arm, an improvement of 5.8 months.

Objective Response Rate (ORR)

Significantly more patients responded to Kadcyla compared to lapatinib plus capecitabine.5,6 The ORR in patients with measurable disease was 43.6% (95% CI, 38.6-48.6) in the Kadcyla arm (n=397) and 30.8% (95% CI, 26.3-35.7, p<0.001) in the lapatinib plus capecitabine arm (n=389).

Key Safety Information

For full safety information, please refer to the Kadcyla Data Sheet available here.7

WARNING: Do not substitute Kadcyla for or with trastuzumab.

In order to prevent medication errors, check the vial labels to ensure the medicine being prepared and administered is Kadcyla (trastuzumab emtansine) and not trastuzumab (Herceptin®).

Enhanced Safety Reporting for Potential Kadcyla-Exposed Pregnancies

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

  • Administration of Kadcyla to pregnant women is not recommended and women should be informed of the possibility of harm to the foetus before they become pregnant. There are no data from the use of Kadcyla in pregnant women.
  • No reproductive and developmental toxicology studies have been conducted with Kadcyla. Trastuzumab, a component of Kadcyla, can cause foetal harm or death when administered to a pregnant woman.
  • In the postmarketing setting, cases of oligohydramnios, some associated with fatal pulmonary hypoplasia, have been reported in pregnant women receiving trastuzumab. Animal studies of maytansine, a closely related chemical entity of the same maytansinoid class as DM1, suggest that DM1, the microtubule inhibiting cytotoxic component of Kadcyla, is expected to be teratogenic and potentially embryotoxic.
  • Verify pregnancy status prior to the initiation of Kadcyla. Women of childbearing potential should use effective contraception while receiving trastuzumab emtansine and for 7 months following the last dose of Kadcyla. Male patients or their female partners should also use effective contraception.
  • If a pregnant woman is treated with Kadcyla, close monitoring by a multidisciplinary team is recommended.
  • It is not known whether Kadcyla is excreted in human milk. Since many medicinal products are excreted in human milk and because of the potential for serious adverse reactions in breastfeeding infants, women should not breastfeed during Kadcyla therapy or for 7 months after the last dose.

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

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

Warnings and Precautions

Pulmonary toxicity

  • Interstitial lung disease (ILD) including pneumonitis, some leading to acute respiratory distress syndrome or fatal outcome, have been reported.
  • Permanently discontinue in patients diagnosed with ILD or pneumonitis.
  • Patients with dyspnoea at rest due to complications of advanced malignancy and co-morbidities may be at increased risk of pulmonary events.

Hepatotoxicity

  • Serious hepatotoxicity, liver failure and death have occurred in patients treated with Kadcyla (refer to monitoring and dose modification guidelines in Data Sheet).
  • Serious hepatobiliary disorders, including nodular regenerative hyperplasia (NRH) of the liver and some with fatal outcome due to drug-induced liver injury have been observed. Permanently discontinue treatment upon diagnosis of NRH.

Left ventricular dysfunction

  • Kadcyla may lead to reductions in LVEF.
  • Symptomatic CHF is a potential risk.
  • Monitor and reduce dose or discontinue as appropriate (refer to monitoring and dose modification guidelines in Data Sheet).

Infusion-related reactions (IRR)

  • Treatment is not recommended in patients who permanently discontinued trastuzumab due to an IRR.
  • Treatment should be interrupted in patients with severe IRR and permanently discontinued in the event of a life threatening IRR.

Hypersensitivity reactions

  • Observe closely for hypersensitivity reactions, especially during first infusion.
  • Medications to treat serious anaphylactic like reactions, as well as emergency equipment, should be available for immediate use.

Thrombocytopenia

  • Bleeding events with a fatal outcome have been observed.
  • Severe cases of haemorrhagic events, including CNS haemorrhage have been reported.
  • Monitor patients with thrombocytopenia and patients on anti-coagulant treatment closely (refer to monitoring and dose modification guidelines in Data Sheet).

Neurotoxicity

  • Treatment should be temporarily discontinued in patients experiencing Grade 3 or 4 peripheral neuropathy until symptoms resolve or improve to ≤ Grade 2.

Extravasation

  • The infusion site should be closely monitored for possible subcutaneous infiltration during administration.
  • Blood and Lymphatic System Disorders: thrombocytopenia, anaemia
  • Gastrointestinal Disorders: nausea, constipation, vomiting, diarrhoea, stomatitis, abdominal pain and dry mouth
  • General Disorders and Administration: fatigue, pyrexia, asthenia, chills
  • Infections and Infestations: urinary tract infection
  • Investigations: transaminases increased, hypokalaemia
  • Musculoskeletal and Connective Tissue Disorders: musculoskeletal pain, arthralgia, myalgia
  • Nervous System Disorders: headache, peripheral neuropathy
  • Psychiatric Disorders: insomnia
  • Respiratory, Thoracic, and Mediastinal Disorders: epistaxis, cough and dyspnoea
  • Skin and Subcutaneous Tissue Disorders: rash
  • Vascular Disorders: haemorrhage

Adverse Effects: (very common only; see Data Sheet for full list)

Pregnancy: Category D

  • Administration to pregnant women is not recommended.
  • See above for Enhanced Safety Reporting for Potential Kadcyla-Exposed Pregnancies.

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

References

  1. Chung CT et al. Goals and objectives in the management of metastatic breast cancer. Oncologist 2013;8:514-520.
  2. Junttila TT et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011;128(2):347-356
  3. Slamon D 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.
  4. Baselga J et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-119.
  5. Verma S et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Engl J Med 2012;367:1783-1791.
  6. Blackwell KL et al. Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. J Clin Oncol (ASCO Annual Meeting Abstracts) 2012;(Suppl):LBA1
  7. Kadcyla® (trastuzumab emtansine) Data Sheet. Available here.

Resources

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

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

Click the image to download the Kadcyla Patient Handbook.

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