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Perjeta

Perjeta is a HER2 dimerisation inhibitor for neoadjuvant (eBC) and advanced breast cancer.

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Please review the Data Sheet before prescribing.

Perjeta is a novel, first in class HER2 dimerisation inhibitor monoclonal antibody, for HER2-positive advanced breast cancer.1

Perjeta is a Prescription Medicine, available as 420mg/14mL single-use vial for intravenous (IV) infusion.1

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

Medsafe-registered indication1

Neoadjuvant Treatment of Breast Cancer

Perjeta is indicated in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of patients with inflammatory or locally advanced HER2-positive breast cancer as part of a complete treatment regimen. Note to indication: this approval is based on improvement in pathological complete response rate. No improvement in disease-free, progression-free or overall survival has been shown.

Metastatic Breast Cancer

Perjeta is indicated in combination with trastuzumab and docetaxel for patients with HER2- positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for their metastatic disease.

A Research Review product review on the use of Perjeta in the neoadjuvant setting can be found below in the linked document. This includes expert commentary from Dr Sheridan Wilson a Medical Oncologist specialising in the treatment of breast cancer & Associate Professor Ian Campbell general and breast cancer surgeon. You can view the article HERE.

Perjeta’s Mechanisms of Action

Perjeta binds to the extracellular dimerisation domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and thereby blocks ligand-dependent heterodimerisation of HER2 with other HER family members, including EGFR, HER3 and HER4. 1

It inhibits ligand initiated intracellular signaling through two major signal pathways, mitogen activated protein (MAP) kinase and phosphoinositide 3 kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. 1

In addition, Perjeta mediates antibody-dependent cell-mediated cytotoxicity (ADCC).1

While Perjeta alone inhibited the proliferation of human tumour cells, the anti-tumour activity was significantly augmented when Perjeta was used in combination with Herceptin in HER2- overexpressing xenograft models. 1




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

Perjeta’s Funding Status

Perjeta is a fully funded medicine for patients with HER2-positive metastatic breast cancer who meet pre-defined criteria.

We provide a Cost Share Programme to assist with the cost of Perjeta for patients with previously-untreated, HER2 positive metastatic breast cancer (mBC) who do not meet PHARMAC funding criteria.

Perjeta is not a PHARMAC funded medicine for the neoadjuvant treatment of eBC.

We provide a Cost Share Programme to assist with the cost of Perjeta for the neoadjuvant treatment of patients with inflammatory or locally advanced HER2-positive breast cancer.

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

Reference

  1. Perjeta® (pertuzumab) Data Sheet. Available here.

The Perjeta Neoadjuvant Cost Share Programme (CSP) assists with the cost of Perjeta for New Zealand patients with inflammatory or locally advanced HER2-positive breast cancer.

The Perjeta Neoadjuvant Cost Share Programme criteria are:

  1. Patient will receive Perjeta in combination with Herceptin (trastuzumab) and chemotherapy for the neoadjuvant treatment of inflammatory or locally advanced HER2-positive breast cancer as part of a complete treatment regimen.
  2. Pricing in the CSP assumes patient receives government reimbursed Herceptin.

The Perjeta Cost Share Programme assists with the cost of Perjeta for New Zealand patients with previously-untreated HER2-positive metastatic breast cancer (mBC). Treatment is to be given in combination with Herceptin® (trastuzumab) and Docetaxel.

The Perjeta Cost Share Programme criteria are:

  1. Patient has previously untreated HER2-positive mBC^ and
  2. Perjeta to be given in combination with Herceptin and Docetaxel

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

Bridging Cost Share Programme from Perjeta to Kadcyla® (trastuzumab emtansine)

For patients who progress on Perjeta and are eligible for Kadcyla® (trastuzumab emtansine) 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 Perjeta and Kadcyla.

Health Insurance Quick Guide


Click on the image below to download a copy of the Perjeta & Kadcyla Cost Share Programme Brochure.


Click on the images below to download copies of the Cost Share Programme Enrolment Form and Claim Form.


Perjeta Neoadjuvant Cost Share Programme Enrolment & Claim Form

PCSP_EnrolmentForm

Perjeta Cost Share Programme Enrolment Form

PCSP_ClaimForm

Perjeta Cost Share Programme Claim Form

Newer agents and combination therapies are needed to overcome drug resistance and extend outcomes for metastatic breast cancer (mBC) patients.

Despite an initial response to Herceptin® (trastuzumab) and taxane therapy, approximately 50% of patients with HER2-positive mBC will develop resistance and experience disease progression within 12 months. However, more recent treatments have improved the survival of patients with this disease.

In the Phase III study involving patients with previously untreated HER2-positive mBC (CLEOPATRA), Perjeta in combination with Herceptin and docetaxel significantly extended median progression free survival by 6.1 months compared to Herceptin and docetaxel alone (18.5 months vs. 12.4 months [p<0.001], respectively; HR=0.62).More than 30% of patients remained on treatment at three years.4

In a confirmatory overall survival (OS) analysis at a median follow-up of 30 months, there was a significant improvement in OS in patients treated with Perjeta, Herceptin, and docetaxel compared to patients treated with Herceptin and docetaxel alone (HR=0.66; p=0.0008).5 Median OS has not been reached in the Perjeta, Herceptin, and docetaxel arm and was 37.6 months in the placebo arm.5

In 2015, the final overall survival analysis from the CLEOPATRA trial was reported at a median of 50 months’ follow up.[i] The authors reported that the addition of pertuzumab to trastuzumab and docetaxel for the treatment of first line metastatic HER2-positive breast cancer improved median OS by 15.7 months compared with trastuzumab and docetaxel plus placebo (56.5 versus 40.8 months, respectively).Overall survival and progression-free survival benefits to the pertuzumab group were maintained compared with previous interim analyses. Rates of adverse events also remained consistent with the primary analysis.The authors commented this duration of OS is “exceptionally long in this population of patients”.


Key Safety Information

For full safety information, please refer to the Perjeta Data Sheet available here.8

Enhanced Safety Reporting for Potential Perjeta-Exposed Pregnancies

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

  • Perjeta should be avoided during pregnancy unless the potential benefit for the mother outweighs the potential risk to the foetus.There are no studies of Perjeta in pregnant women and the safe use of Perjeta during pregnancy and lactation has not been established.
  • Verify pregnancy status prior to the initiation of Perjeta. Women of child bearing potential should use effective contraception while receiving Perjeta and for 6 months following the last dose of Perjeta.
  • Patients who become pregnant during Perjeta therapy or within 6 months following the last dose of Perjeta should be closely monitored for oligohydramnios.


If Perjeta is used during pregnancy or if a patient becomes pregnant while being treated with Perjeta or within 6 months following the last dose of Perjeta, immediately report the exposure to Roche on 0800276 243 or email nz.drugsafety@roche.com.

Additional information will be requested during a Perjeta-exposed pregnancy and the first year of the infant’s life. This will enable Roche to better understand the safety of Perjeta and to provide appropriate information to Health Authorities, Healthcare Providers and patients.


Cardiac Adverse Events (AEs)

The frequency of cardiac AEs did not increase with the addition of Perjeta to Herceptin and docetaxel.4,5,8 Cardiac adverse events were largely reversible, and clinically manageable.8

Figure 1: Incidence of cardiac events with the addition of Perjeta to Herceptin and docetaxel vs Herceptin plus docetaxel alone.


Precautions

Left ventricular dysfunction:

  • Assess LVEF prior to initiation of treatment and regularly during treatment.
  • Patients who have received prior anthracyclines or prior chest wall radiotherapy may be at higher risk of decreased LVEF.
  • If LVEF <40%, or 40-45% and ≥10% points below baseline, withhold treatment and repeat LVEF assessment within 3 weeks. Discontinue if no improvement or further decline unless benefit outweighs risk.

Infusion-related reactions

  • Observe patient during, and for 60min after first infusion and for 30min for subsequent infusions.
  • If significant reaction occurs, slow or interrupt infusion and administer appropriate therapy.
  • Consider permanent discontinuation with severe infusion reactions.

Hypersensitivity reactions/anaphylaxis

  • Severe hypersensitivity, including anaphylaxis, has been observed.
  • Closely observe patients for hypersensitivity reactions.
  • Medicines and emergency equipment should be available for immediate use.

Febrile neutropenia

  • Increased risk of febrile neutropenia with Perjeta combination therapy.
  • May be associated with higher incidence of mucositis and diarrhoea.
  • Highest proportion in first cycle and declined steadily thereafter.

Pregnancy (Category D):

  • Should be avoided during treatment and for 6 months after last dose (contraception advised).
  • Nursing mothers: avoid breast-feeding during treatment and for 6 months after the last dose.

Adverse Effects (very common only (≥10%); see Data Sheet for full list)

  • General disorders: fatigue, asthenia, mucosal inflammation, pyrexia, peripheral oedema.
  • Skin/SC disorders: alopecia, rash, nail disorder, pruritus, dry skin.
  • GI disorders: diarrhoea, nausea, dyspepsia, vomiting, constipation, stomatitis.
  • Blood/lymph disorders: neutropenia, anaemia, leukopenia, febrile neutropenia.
  • Nervous system disorders: peripheral neuropathy, headache, dysgeusia, peripheral sensory neuropathy, dizziness.
  • Musculoskeletal/CT disorders: myalgia, arthralgia, pain in extremity.
  • Infections/Infestations: upper respiratory tract infection, nasopharyngitis.
  • Respiratory/thoracic disorders: cough, dyspnoea.
  • Metabolism/nutrition disorders: decreased appetite.
  • Eye disorders: increased lacrimation.
  • Psychiatric disorders: insomnia.

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

References

  1. Roche H and Vahdat LT. Treatment of metastatic breast cancer: second line and beyond.Ann Oncology 2011;22:1000-1010.
  2. 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.
  3. Baselga J et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.N Engl J Med 2012;366:109-119.
  4. Swain SM et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.Oncologist 2013;18:257-64
  5. Verma S et al. Trastuzumab emtansine for HER2-positive advanced breast cancer.N Engl J Med 2012;367:1783-1791.
  6. Swain SM, Baselga J, Kim S-B, et al.Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer.N Engl J Med 2015;372:724-34.
  7. Perjeta® (pertuzumab) Data Sheet.Available here.

This patient booklet is a helpful source of information to support patients throughout their treatment. It is not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

More patient information on Perjeta 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 patient booklet ‘What does my pathology report mean?’


Click on the image to download a Research Review product review on the use of Perjeta in the neoadjuvant setting.