PHESGO Solution for injection Ref.[51368] Active ingredients: Pertuzumab Pertuzumab and Trastuzumab Trastuzumab

Phesgo should only be initiated under the supervision of a physician experienced in the administration of anti-cancer agents. Phesgo should be administered by a healthcare professional prepared to manage anaphylaxis and in an environment where full resuscitation facilities are immediately available (see section 4.4).

In order to prevent medication errors, it is important to check the vial label to ensure that the medicinal product being prepared and administered is Phesgo.

Patients currently receiving intravenous pertuzumab and trastuzumab can switch to Phesgo. Switching treatment from intravenous pertuzumab and trastuzumab to Phesgo (or vice versa) was investigated in study MO40628 (see sections 4.8 and 5.1).

Posology

Patients treated with Phesgo must have HER2-positive tumour status, defined as a score of 3+ by immunohistochemistry (IHC) and/or a ratio of ≥2.0 by in situ hybridization (ISH), assessed by a validated test.

To ensure accurate and reproducible results, the testing must be performed in a specialized laboratory, which can ensure validation of the testing procedures. For full instructions on assay performance and interpretation, please refer to the package leaflet of validated HER2 testing assays.

For Phesgo dose recommendations in early and metastatic breast cancer please refer to Table 1.

Table 1. Phesgo recommended dosing and administration:

^a Patients should be observed for injection-related reactions and hypersensitivity reactions
^b Observation period should start following administration of Phesgo and be completed prior to any subsequent administration of chemotherapy

In patients receiving a taxane, Phesgo should be administered prior to the taxane.

When administered with Phesgo, the recommended initial dose of docetaxel is 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 Phesgo in the adjuvant setting, the recommended dose of paclitaxel is 80 mg/m² once weekly for 12 weekly cycles.

In patients receiving an anthracycline-based regimen, Phesgo should be administered following completion of the entire anthracycline regimen (see section 4.4).

Metastatic breast cancer

Phesgo should be administered in combination with docetaxel. Treatment with Phesgo may continue until disease progression or unmanageable toxicity even if treatment with docetaxel is discontinued (see section 4.4).

Early breast cancer

In the neoadjuvant setting, Phesgo should be administered for 3 to 6 cycles in combination with chemotherapy, as part of a complete treatment regimen for early breast cancer (see section 5.1).

In the adjuvant setting, Phesgo should be administered 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. Phesgo should start on Day 1 of the first taxanecontaining cycle and should continue even if chemotherapy is discontinued.

Delayed or missed doses

If the time between two sequential injections is:

• less than 6 weeks, the maintenance dose of Phesgo 600 mg/600 mg should be administered as soon as possible. Thereafter, continue with the 3-weekly schedule.
• 6 weeks or more, a loading dose of Phesgo 1200 mg/600 mg should be re-administered followed by maintenance dose of Phesgo 600 mg/600 mg every 3 weeks thereafter.

Dose modifications

Dose reductions are not recommended for Phesgo. Discontinuation of treatment with Phesgo may be needed at the discretion of the physician.

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 summary of product characteristics (SmPC).

Switching from intravenous pertuzumab and trastuzumab administration to Phesgo

• In patients receiving intravenous pertuzumab and trastuzumab with less than 6 weeks since their last dose, Phesgo should be administered as a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab and every 3 weeks for subsequent administrations.
• In patients receiving intravenous pertuzumab and trastuzumab with 6 weeks or more since their last dose, Phesgo should be administered as a loading dose of 1200 mg pertuzumab/600 mg trastuzumab, followed by a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab every 3 weeks for subsequent administrations.

Left ventricular dysfunction

Phesgo should be withheld for at least 3 weeks for any signs and symptoms suggestive of congestive heart failure. Phesgo should be discontinued if symptomatic heart failure is confirmed (see section 4.4 for more details).

Patients with metastatic breast cancer

Patients should have a pre-treatment left ventricular ejection fraction (LVEF) of ≥50%. Phesgo 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.

Phesgo may be resumed if the LVEF has recovered to >45%, or to 40-45% associated with a difference of <10% points below pre-treatment values.

Patients with early breast cancer

Patients should have a pre-treatment LVEF of ≥55% (≥50% after completion of the anthracycline component of chemotherapy, if given).

Phesgo should be withheld for at least 3 weeks for a drop in LVEF to less than 50% associated with a fall of ≥10% points below pre-treatment values.

Phesgo may be resumed if the LVEF has recovered to ≥50% or to a difference of <10% points below pre-treatment values.

Special populations

Elderly

No overall differences in efficacy of Phesgo were observed in patients ≥65 and <65 years of age. No dose adjustment of Phesgo is required in patients ≥65 years of age. Limited data are available in patients >75 years of age.

Please see section 4.8 for assessment of safety in elderly patients.

Renal impairment

Dose adjustments of Phesgo are not needed in patients with mild or moderate renal impairment. No dose recommendations can be made for patients with severe renal impairment because of the limited pharmacokinetic (PK) data available (see section 5.2).

Hepatic impairment

The safety and efficacy of Phesgo have not been studied in patients with hepatic impairment. Patients with hepatic impairment are unlikely to require Phesgo dose adjustment. No specific dose adjustment are recommended (see section 5.2).

Paediatric population

The safety and efficacy of Phesgo in children and adolescents below 18 years of age have not been established. There is no relevant use of Phesgo in the paediatric population in the indication of breast cancer.

Method of administration

Phesgo should be administered as a subcutaneous injection only. Phesgo is not intended for intravenous administration.

The injection site should be alternated between the left and right thigh only. New injections should be given at least 2.5 cm from the previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard. The dose should not be split between two syringes or between two sites of administration. During the treatment course with Phesgo, other medicinal products for subcutaneous administration should preferably be injected at different sites.

The loading dose and maintenance dose should be administered over 8 and 5 minutes, respectively.

An observation period of 30 minutes after completion of Phesgo loading dose and 15 minutes after completion of the maintenance dose is recommended for injection-related reactions (see sections 4.4 and 4.8).

Injection-related reactions

The injection may be slowed or paused if the patient experiences injection-related symptoms (see section 4.4 and section 4.8). Treatment including oxygen, beta agonists, antihistamines, rapid intravenous fluids and antipyretics may also help alleviate systemic symptoms.

Hypersensitivity reactions / anaphylaxis

The injection should be discontinued immediately and permanently if the patient experiences a NCICTCAE Grade 4 reaction (anaphylaxis), bronchospasm or acute respiratory distress syndrome (see section 4.4 and section 4.8).

For instructions on use and handling of the medicinal product before administration, see section 6.6.

The highest Phesgo dose tested is 1200 mg pertuzumab/600 mg trastuzumab. In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.

18 months.

Once transferred from the vial to the syringe the medicinal product is physically and chemically stable for 28 days at 2°C-8°C protected from light and for 24 hours (cumulative time in the vial and the syringe) at ambient temperature (maximum 30°C) in diffused daylight.

As Phesgo does not contain any antimicrobial-preservative, from a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless preparation of the syringe has taken place in controlled and validated aseptic conditions.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

For storage conditions of the opened medicinal product, see sections 6.3 and 6.6

Phesgo 600 mg/600 mg solution for injection

Pack of one 15 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper, containing 10 mL solution of 600 mg of pertuzumab and 600 mg of trastuzumab. The stopper is sealed with aluminium and covered by an orange plastic flip-off cap.

Phesgo 1200 mg/600 mg solution for injection

Pack of one 20 mL type I borosilicate glass vial tapered with fluororesin-laminated rubber stopper, containing 15 mL solution of 1200 mg of pertuzumab and 600 mg of trastuzumab. The stopper is sealed with aluminum and covered by a cool green plastic flip-off cap.

Phesgo should be inspected visually to ensure there is no particulate matter or discolouration prior to the administration. If particulate matter or discoloration is observed the vial should be discarded per local disposal guidelines.

Do not shake the vial.

A syringe, a transfer needle and an injection needle are needed to withdraw Phesgo solution from the vial and inject it subcutaneously. Phesgo may be injected using hypodermic injection needles with gauges between 25G-27G and lengths between 3/8"(10 mm)-5/8"(16 mm). Phesgo is compatible with stainless steel, polypropylene, polycarbonate, polyethylene, polyurethane, polyvinyl chloride and fluorinated ethylene polypropylene.

As Phesgo does not contain any antimicrobial-preservative, from a microbiological point of view, the medicinal product should be used immediately. If not used immediately, preparation should take place in a controlled and validated aseptic conditions. After transfer of the solution to the syringe, it is recommended to replace the transfer needle by a syringe closing cap to avoid drying of the solution in the syringe and not compromise the quality of the medicinal product. Label the syringe with the peeloff sticker. The hypodermic injection needle must be attached to the syringe immediately prior to administration followed by volume adjustment to 15 mL if Phesgo 1200 mg/600 mg is used or 10 mL if Phesgo 600 mg/600 mg is used.

Phesgo is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.