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Perjeta is a brand name for Pertuzumab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Early breast cancer Perjeta is indicated for use in combination with trastuzumab and chemotherapy in: • the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer at high risk of recurrence (see section 5.1) • the adjuvant treatment of adult patients…
Verbatim from this product's EMA label. Tap a section to expand.
Perjeta should only be initiated under the supervision of a physician experienced in the administration of anti-cancer agents. Perjeta should be administered by a healthcare professional prepared to manage anaphylaxis and in an environment where full resuscitation facilities are immediately available.
0 by in situ hybridisation (ISH) assessed by a validated test. 3 To ensure accurate and reproducible results, the testing must be performed in a specialised laboratory, which can ensure validation of the testing procedures. For full instructions on assay performance and interpretation please refer to the package leaflets of validated HER2 testing assays.
The recommended initial loading dose of pertuzumab is 840 mg administered as a 60 minute intravenous infusion, followed every 3 weeks thereafter by a maintenance dose of 420 mg administered over a period of 30 to 60 minutes. An observation period of 30 - 60 minutes is recommended after completion of each infusion.
4). Perjeta and trastuzumab should be administered sequentially and not mixed in the same infusion bag. Perjeta and trastuzumab can be given in any order. When administered with Perjeta the recommendation is to follow a 3 weekly schedule for trastuzumab administered as either: • an IV infusion with an initial loading dose of trastuzumab 8 mg/kg body weight followed every 3 weeks thereafter by a maintenance dose of 6 mg/kg body weight or • a fixed subcutaneous dose of trastuzumab by injection (600 mg) every 3 weeks irrespective of the patient’s body weight.
In patients receiving a taxane, Perjeta and trastuzumab should be administered prior to the taxane. When administered with Perjeta, docetaxel can be started at 75 mg/m2, and subsequently escalated to 100 mg/m2 depending on the chosen regimen and tolerability of the initial dose.
Alternatively, docetaxel can be given at 100 mg/m2 on a 3 weekly schedule from the start, again depending on the chosen regimen. If a carboplatin-based regimen is used, the recommended dose for docetaxel is 75 mg/m2 throughout (no dose escalation).
When administered with Perjeta in the adjuvant setting, the recommended dose of paclitaxel is 80 mg/m2 once weekly for 12 weekly cycles. 4). Metastatic breast cancer Perjeta should be administered in combination with trastuzumab and docetaxel .
Summary of the safety profile The safety of Perjeta has been evaluated in more than 6,000 patients in Phase I, II, and III trials in patients with various malignancies and predominantly treated with Perjeta in combination with other antineoplastic agents.
Those studies included the pivotal trials CLEOPATRA (n=808), NEOSPHERE (n=417), TRYPHAENA (n=225), and APHINITY (n=4804) [pooled in Table 2]. The safety of Perjeta was generally consistent across studies, although the incidence and most common adverse drug reactions (ADRs) varied depending on whether Perjeta was administered as monotherapy or with concomitant anti-neoplastic agents.
Tabulated list of adverse reactions Table 2 summarizes the ADRs from the Perjeta-treated groups of the following pivotal clinical trials: • CLEOPATRA, in which Perjeta was given in combination with docetaxel and trastuzumab to patients with metastatic breast cancer (n=453) • NEOSPHERE (n=309) and TRYPHAENA (n=218), in which neoadjuvant Perjeta was given in combination with trastuzumab and chemotherapy to patients with locally advanced, inflammatory, or early breast cancer • APHINITY, in which adjuvant Perjeta was given in combination with trastuzumab and anthracycline-based or non-anthracycline-based, taxane-containing chemotherapy to patients with early breast cancer (n=2364) 9 In addition, ADRs reported in the post-marketing setting are included in Table 2.
As Perjeta was used with trastuzumab and chemotherapy in these trials, it is difficult to ascertain the causal relationship of an adverse event to a particular medicinal product. The ADRs are listed below by MedDRA system organ class (SOC) and categories of frequency: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon( ≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Not known (cannot be estimated from the available data) Within each frequency grouping and SOC, ADRs are presented in the order of decreasing seriousness.
Traceability In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded. Left ventricular dysfunction (including congestive heart failure) Decreases in LVEF have been reported with medicinal products that block HER2 activity, including Perjeta.
The incidence of symptomatic left ventricular systolic dysfunction (LVD) [congestive heart failure] was higher in patients treated with Perjeta in combination with trastuzumab and chemotherapy compared with trastuzumab and chemotherapy .
Patients who have received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of LVEF declines. 8). Perjeta has not been studied in patients with: a pre-treatment LVEF value of < 50%; a prior history of congestive heart failure (CHF); LVEF declines to < 50% during prior trastuzumab adjuvant therapy; or conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment or a cumulative prior anthracycline exposure to > 360 mg/m2 of doxorubicin or its equivalent.
g. once during neoadjuvant treatment and every 12 weeks in the adjuvant or metastatic setting) to ensure that LVEF is within normal limits. 2 and has not improved, or has declined further at the subsequent assessment, discontinuation of Perjeta and trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks.
Cardiac risk should be carefully considered and balanced against the medical need of the individual patient before use of Perjeta with an anthracycline. Based on the pharmacological actions of HER2-targeted agents and anthracyclines, the risk of cardiac toxicity might be expected to be higher with concomitant use of Perjeta and anthracyclines than with sequential use.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Treatment with Perjeta and trastuzumab may continue until disease progression or unmanageable toxicity even if treatment with docetaxel is discontinued. 1). In the adjuvant setting, Perjeta should be administered in combination with trastuzumab for a total of one year (up to 18 cycles or until disease recurrence, or unmanageable toxicity, whichever occurs first) as part of a complete regimen for early breast cancer and regardless of the timing of surgery.
Treatment should include standard anthracycline- and/or taxane-based chemotherapy. Perjeta and trastuzumab should start on Day 1 of the first taxane-containing cycle and should continue even if chemotherapy is discontinued. Delayed or missed doses For recommendations on delayed or missed doses, please refer to Table 1 below.
4 Table 1 Recommendations regarding delayed or missed doses Time between two sequential infusions Perjeta trastuzumab IV SC < 6 weeks The 420 mg dose of pertuzumab should be administered as soon as possible. Do not wait until the next planned dose.
Thereafter, revert to the original planned schedule. The 6 mg/kg dose of trastuzumab IV should be administered as soon as possible. Do not wait until the next planned dose. Thereafter, revert to the original planned schedule. The fixed dose of 600 mg trastuzumab SC should be administered as soon as possible.
Do not wait until the next planned dose. ≥ 6 weeks The 840 mg loading dose of pertuzumab should be re-administered as a 60 minute infusion, followed by a maintenance dose of 420 mg IV administered every 3 weeks thereafter. The loading dose of 8 mg/kg of trastuzumab IV should be re- administered over approximately 90 minutes, followed by a maintenance dose of 6 mg/kg IV administered every 3 weeks thereafter.
Dose modification Dose reductions are not recommended for Perjeta or trastuzumab. For details regarding trastuzumab, please refer to the summary of product characteristics (SmPC). Patients may continue therapy during periods of reversible chemotherapy-induced myelosuppression but they should be monitored carefully for complications of neutropenia during this time.
For docetaxel and other chemotherapy dose modifications, see relevant SmPC. If trastuzumab treatment is discontinued, treatment with Perjeta should be discontinued. Left ventricular dysfunction Perjeta and trastuzumab should be withheld for at least 3 weeks for any signs and symptoms suggestive of congestive heart failure.
4 for more details). Patients with metastatic breast cancer Patients should have a pre-treatment left ventricular ejection fraction (LVEF) of ≥ 50%. Perjeta and trastuzumab should be withheld for at least 3 weeks for: • a drop in LVEF to less than 40% • a LVEF of 40%-45% associated with a fall of ≥ 10% points below pre-treatment value.
Perjeta and trastuzumab may be resumed if the LVEF has recovered to > 45%, or to 40-45% associated with a difference of < 10% points […]
The most common ADRs (≥30%) from this pooled data were diarrhoea, alopecia, nausea, fatigue, neutropenia, and vomiting. The most common NCI-CTCAE Grade 3-4 ADRs (≥10%) were neutropenia and febrile neutropenia. Table 2 Summary of ADRs in patients treated with Perjeta in clinical trials^, and in the Post- marketing setting† System organ class Very Common Common Uncommon Rare Infections and infestations Nasopharyngitis Paronychia Upper respiratory tract infection Blood and lymphatic system disorders Febrile neutropenia* Neutropenia Leucopenia Anaemia Immune system disorders Infusion-related reaction°°, * Hypersensitivity°, * Drug hypersensitivity°, * Anaphylactic reaction°, * Cytokine release syndrome°° Metabolism and nutrition disorders Decreased appetite Tumour lysis syndrome† Psychiatric disorders Insomnia Nervous system disorders Neuropathy peripheral Headache Dysgeusia Peripheral sensory neuropathy Dizziness Paraesthesia Eye disorders Lacrimation increased Cardiac disorders Left ventricular dysfunction ** Cardiac failure congestive** Vascular disorders Hot flush Respiratory, thoracic and mediastinal disorders Cough Epistaxis Dyspnoea Interstitial lung disease Pleural effusion Gastrointestinal disorders Diarrhoea Vomiting Stomatitis Nausea 10 System organ class Very Common Common Uncommon Rare Constipation Dyspepsia Abdominal pain Skin and subcutaneous tissue disorders Alopecia Rash Nail disorder Pruritus Dry skin Musculoskeletal and connective tissue disorders Myalgia Arthralgia Pain in extremity General disorders and administration site conditions Mucosal inflammation Oedema peripheral Pyrexia Fatigue Asthenia Chills Pain Oedema ^ Table 2 shows pooled data from the overall treatment period in CLEOPATRA (data cutoff 11 February 2014; median number of cycles of Perjeta was 24); and from the neoadjuvant treatment period in NEOSPHERE (median number of cycles of Perjeta was 4, across all treatment arms) and TRYPHAENA (median number of cycles of Perjeta was 3 – 6 across treatment arms) and from the treatment period of APHINITY (median number of cycles of Perjeta was 18).
* ADRs with a fatal outcome have been reported. ** For the overall treatment period across the 4 studies. The incidence of left ventricular dysfunction and cardiac failure congestive reflect the MedDRA Preferred Terms reported in the individual studies.
° Hypersensitivity/anaphylactic reaction is based on a group of terms. °° Infusion-related reaction (IRRs) includes a range of different terms within a time window, see “Description of selected adverse reactions” below. 6%, respectively).
8% in the placebo-treated group vs. 4). 9%). There was one case of symptomatic LVD in the Perjeta and trastuzumab-treated group. 6% in the group treated with Perjeta in combination with TCH (docetaxel, carboplatin and trastuzumab). 3% in the group treated with […]
Sequential use of Perjeta (in combination with trastuzumab and a taxane) has been evaluated following the epirubicin or doxorubicin component of many anthracycline-based regimens in the APHINITY and BERENICE studies. However, only limited safety data are available on concurrent use of Perjeta and an anthracycline.
1). Only chemotherapy-naive patients were treated and they received low cumulative doses of epirubicin (up to 300 mg/m2). In this study, cardiac safety was similar to that observed in patients given the same regimen but with Perjeta administered sequentially (following FEC chemotherapy).
8). Close observation of the patient during and for 60 minutes after the first infusion and during and for 30-60 minutes after subsequent infusions of Perjeta is recommended. If a significant infusion-related reaction occurs, the infusion should be slowed down or interrupted and appropriate medical therapies should be administered.
Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be considered in patients with severe infusion-related reactions. 2). Hypersensitivity reactions/anaphylaxis Patients should be observed closely for hypersensitivity reactions.
8). Medicinal products to treat such reactions, as well as emergency equipment, should be available for immediate use. 2). 8). In the CLEOPATRA trial in metastatic breast cancer, nadir neutrophil counts were similar in Perjeta-treated and placebo-treated patients.
The higher incidence of febrile neutropenia in Perjeta-treated patients was associated with the higher incidence of mucositis and diarrhoea in these patients. Symptomatic treatment for mucositis and diarrhoea should be considered. No events of febrile neutropenia were reported after cessation of docetaxel.
Diarrhoea Perjeta may elicit severe diarrhoea. Diarrhoea is most frequent during concurrent administration with taxane therapy. Elderly patients (> 65 years) have a higher risk of diarrhoea compared with younger patients (< 65 years).
Treat diarrhoea according to standard practice and guidelines. Early intervention with loperamide, fluids and electrolyte replacement should be considered, particularly in elderly patients, and in case of severe or prolonged diarrhoea.
Interruption of treatment with pertuzumab should be considered if no improvement in the patient’s condition is achieved. When the diarrhoea is under control treatment with pertuzumab may be reinstated. Excipients with known effect Perjeta contains less than 1 mmol of sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
Perjeta contains polysorbate 20. 8 mg of polysorbate 20. […]