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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/589130/2015

EMEA/H/C/002547

EPAR summary for the public

Perjeta

pertuzumab

This is a summary of the European public assessment report (EPAR) for Perjeta. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Perjeta.

What is Perjeta?

Perjeta is a cancer medicine that contains the active substance pertuzumab. It is available as a concentrate to be made into a solution for infusion (drip) into a vein.

What is Perjeta used for?

Perjeta is used to treat adults with breast cancer which is 'HER2-positive' (where a specific protein called 'HER2' is found on the surface of the cancer cells).

Perjeta can be used to treat metastatic breast cancer (cancer that has spread to other parts of the body) that has not already been treated with chemotherapy medicines or medicines designed to attach to HER2, or breast cancer that has come back after treatment and cannot be removed by surgery. In these cases, Perjeta is used together with trastuzumab and docetaxel (other cancer medicines).

Perjeta can also be used to treat earlier stages of breast cancer at high risk of coming back (i.e. locally advanced, inflammatory or early stage breast cancer), before the patient undergoes surgery. In these cases, Perjeta is used with trastuzumab and chemotherapy.

The medicine can only be obtained with a prescription.

How is Perjeta used?

Treatment with Perjeta should only be started under the supervision of a doctor who is experienced in using cancer medicines and in a hospital setting where resuscitation equipment is available. The HER2-

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positive status of the patient's cancer must be determined in advance of treatment with Perjeta by suitable tests.

Perjeta is given by infusion into a vein. The recommended first dose is 840 mg given over a period of one hour. This is followed by a dose of 420 mg every three weeks given over a period of half an hour to one hour. When used in the earlier stages of breast cancer, treatment with Perjeta should continue until the patient undergoes surgery. For metastatic cancer, treatment should continue until the disease gets worse or the side effects become unmanageable. Treatment should be temporarily interrupted if the patient experiences certain side effects.

How does Perjeta work?

The active substance in Perjeta, pertuzumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Pertuzumab has been designed to recognise and attach to HER2, a protein found on the surface of HER2-positive cancer cells. By attaching to HER2, pertuzumab stops HER2 producing signals that cause the cancer cells to grow. It also activates cells of the immune system, which then kill the cancer cells.

How has Perjeta been studied?

Perjeta has been studied in one main study involving 808 adults with previously untreated HER2-positive metastatic breast cancer. The effects of Perjeta were compared with placebo (a dummy treatment) when given together with other cancer medicines (trastuzumab and docetaxel). The patients were treated until their disease got worse or the side effects of treatment became unmanageable. The main measure of effectiveness was progression free survival (how long the patients lived without their disease getting worse).

Perjeta has also been studied in two main studies involving a total of 642 patients with earlier stages of breast cancer who were to undergo surgery. In these studies, Perjeta was given with trastuzumab and/or chemotherapy. The studies looked at how many patients responded to treatment (i.e. patients who had no cancer cells in the breast after surgery).

What benefit has Perjeta shown during the studies?

In the study in metastatic disease, patients treated with Perjeta lived for longer without their disease getting worse than patients given placebo. On average, patients treated with Perjeta lived for 18.5 months without their disease getting worse, compared with 12.4 months for patients given placebo.

In the studies in patients with earlier stages of breast cancer who were to undergo surgery, Perjeta was shown to improve response to treatment. In the first study, 46% of the patients treated with Perjeta plus trastuzumab and docetaxel responded to treatment, compared with 29% of patients who received trastuzumab and docetaxel alone. Response to treatment was also high in the second study (ranging from 57% to 66%) where Perjeta was given with trastuzumab and different chemotherapy medicines.

What is the risk associated with Perjeta?

The most common side effects with Perjeta given with trastuzumab and chemotherapy are diarrhoea, alopecia (hair loss), nausea (feeling sick) and neutropenia (low levels of neutrophils, a type of white

Perjeta

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blood cell important for fighting infections), which were experienced by more than half of all patients. The most common serious side effects include febrile neutropenia (low levels of neutrophils with fever), serious diarrhoea, leucopenia (low white blood cell counts) and neutropenia. Several other side effects are seen in more than 1 patient in 10.

For the full list of all side effects and restrictions with Perjeta, see the package leaflet.

Why has Perjeta been approved?

The CHMP noted that HER2-positive breast cancer is an aggressive form of breast cancer which occurs in around one in five cases. The Committee considered that Perjeta has been shown to benefit patients with metastatic cancer by extending the amount of time patients lived without their disease getting worse as well as how long they lived. It considered that this would provide an additional benefit when added to other medicines for HER2-positive cancer, notably trastuzumab. Perjeta has also been shown to improve the outcome of patients with earlier stages of breast cancer, when used with trastuzumab and chemotherapy.

The CHMP considered that, despite the side effects reported with Perjeta, the overall safety profile was acceptable. Therefore the CHMP decided that Perjeta's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Perjeta?

A risk management plan has been developed to ensure that Perjeta is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Perjeta, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Perjeta will carry out two studies to assess the effects of using Perjeta and trastuzumab together with two different types of cancer medicine, in patients with HER2-positive breast cancer that is metastatic or has come back after treatment.

The company will also carry out two further studies to look into the long-term benefits and safety of Perjeta when used in patients with earlier stages of breast cancer.

Other information about Perjeta

The European Commission granted a marketing authorisation valid throughout the European Union for Perjeta on 4 March 2013.

The full EPAR for Perjeta can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Perjeta, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 07-2015.

Perjeta

EMA/589130/2015