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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/353945/2016

EMEA/H/C/000582

EPAR summary for the public

Avastin

bevacizumab

This is a summary of the European public assessment report (EPAR) for Avastin. 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 Avastin.

What is Avastin?

Avastin is a cancer medicine that contains the active substance bevacizumab. It is available as a

concentrate that is made up into a solution for infusion (drip) into a vein.

What is Avastin used for?

Avastin is used to treat adults with the following types of cancer in combination with other cancer

medicines:

•    cancer of the colon or rectum (large intestine) that is metastatic (has spread to other parts of the body), in combination with chemotherapy medicines that include a 'fluoropyrimidine';

•    metastatic breast cancer, in combination with paclitaxel or capecitabine;

•    advanced non-small cell lung cancer in patients whose cancer cells are not mainly of the squamous type, where it is given with platinum-based chemotherapy;

•    advanced non-small cell lung cancer in patients whose cancer cells have a certain change ('activating mutations') in the gene for a protein called EGFR, where it is given in combination with erlotinib;

•    advanced or metastatic kidney cancer, in combination with interferon alfa-2a;

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•    epithelial cancer of the ovary, cancer of the fallopian tube (that connect the ovaries to the uterus) or the peritoneum (the membrane lining the abdomen). Avastin is used when the cancer is advanced or recurrent, in combination with certain chemotherapy medicines;

•    cancer of the cervix (the neck of the womb) that is persistent, recurrent or metastatic. Avastin is given in combination with paclitaxel and either the platinum-based medicine cisplatin or, if this cannot be used, another chemotherapy medicine, topotecan.

See the summary of product characteristics (also part of the EPAR) for more information.

The medicine can only be obtained with a prescription.

How is Avastin used?

Avastin treatment should be supervised by a doctor who has experience in the use of cancer treatments.

The first infusion of Avastin should last 90 minutes, but subsequent infusions may be given more quickly if the first infusion is tolerated well. The dose is between 5 and 15 mg per kilogram body weight every two or three weeks, depending on the type of cancer being treated. The treatment is continued until the patient no longer benefits from it. The doctor may decide to interrupt or stop treatment if the patient develops certain side effects.

How does Avastin work?

The active substance in Avastin, bevacizumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to vascular endothelial growth factor (VEGF), a protein that circulates in the blood and makes blood vessels grow. By attaching to VEGF, Avastin stops it having an effect. As a result, the cancer cells cannot develop their own blood supply and are starved of oxygen and nutrients, helping to slow down the growth of tumours.

How has Avastin been studied?

In metastatic cancer of the colon or rectum, the effects of adding Avastin to chemotherapy including a fluoropyrimidine have been studied in three main studies. The first two studies involved patients whose metastatic disease was being treated for the first time ('first-line' treatment): the first study (in 923 patients) and the second study (in 1,401 patients) compared Avastin with placebo (a dummy treatment) when given in combination with chemotherapy. The third study involved 829 patients who had failed previous treatment including a fluoropyrimidine and irinotecan (other chemotherapy medicines).

In metastatic breast cancer, Avastin has been studied in two main studies. The first study compared the effects of Avastin with paclitaxel to paclitaxel alone in 722 patients. The second study compared the effects of adding either Avastin or placebo to various chemotherapy treatments, including capecitabine, in 1,237 patients.

In advanced, metastatic or recurrent lung cancer, Avastin has been studied in 878 patients whose cancer cells are mainly non-squamous. This study compared Avastin plus platinum-based chemotherapy with chemotherapy alone.

In patients with a certain subtype of non-small cell lung cancer with activating mutations in the EGFR gene, a study in 152 patients compared Avastin plus erlotinib with erlotinib alone.

Avastin

In advanced or metastatic kidney cancer, Avastin has been studied in 649 patients with advanced or metastatic disease. The study compared Avastin with placebo when given in combination with interferon alfa-2a.

In ovarian, fallopian tube and peritoneal cancer, two main studies were performed involving 3,401 patients with newly diagnosed cancer including advanced cancer. In these studies, Avastin, in combination with carboplatin and paclitaxel, was compared with carboplatin and paclitaxel alone.

Two further studies in ovarian, fallopian tube and peritoneal cancers were performed in a total of 845 patients with recurrent cancer (that came back after previous platinum-based chemotherapy). The first study included patients whose cancer came back 6 months or more after previous treatment ('platinum-sensitive disease'), while the second study was in patients with more aggressive cancer that had come back within 6 months of previous treatment ('platinum-resistant disease'). These studies looked at the effect of adding Avastin to a combination treatment with carboplatin and gemcitabine or to paclitaxel, topotecan, or pegylated liposomal doxorubicin.

In cancer of the cervix, one main study involving 452 patients with advanced persistent, recurrent or metastatic disease was carried out. The study compared the effect of adding Avastin to chemotherapy using paclitaxel plus cisplatin or topotecan to results in patients given chemotherapy alone.

In all of the studies, the main measure of effectiveness was either overall survival (how long the patients lived) or progression-free survival (how long the patients lived without their disease getting worse).

What benefit has Avastin shown during the studies?

In metastatic cancer of the colon or rectum, Avastin increased both overall and progression-free survival when it was added to fluoropyrimidine-containing chemotherapy. In the first study of previously untreated patients, the average overall survival was 20.3 months in the patients adding Avastin and 15.6 months in those receiving chemotherapy alone. In the second study, progression-free survival was 9.4 months in the patients receiving Avastin and 8.0 months in those receiving placebo.

In previously treated patients, overall survival was 12.9 months in the patients adding Avastin and 10.8 months in those receiving chemotherapy alone.

In metastatic breast cancer, adding Avastin also increased progression-free survival. When it was added to paclitaxel, the average progression-free survival was 11.4 months, compared with 5.8 months in those receiving paclitaxel alone. When Avastin was added to capecitabine, the average progression-free survival was 8.6 months, compared with 5.7 months in those receiving capecitabine with placebo.

In advanced, metastatic or recurrent lung cancer, the average overall survival was 12.3 months in the patients taking Avastin with platinum-based chemotherapy, and 10.3 months for those taking chemotherapy alone.

In the lung cancer study in patients with activating EGFR mutations, patients on Avastin plus erlotinib had progression-free survival of 16.0 months on average compared with 9.7 months in patients given erlotinib alone.

In advanced or metastatic kidney cancer, the average progression-free survival was 10.2 months in the patients receiving Avastin and 5.4 months in those receiving placebo.

In the studies in newly diagnosed ovarian, fallopian tube and peritoneal cancer, average progressionfree survival was 19.3 months with Avastin versus 16.9 months with carboplatin and paclitaxel alone in one study, and 14.7 months versus 10.6 months in the second study.

Avastin

In the study of ovarian, fallopian tube and peritoneal cancer that came back 6 month or more after previous chemotherapy, average progression-free survival was 12.4 months when Avastin was added to carboplatin and gemcitabine, compared with 8.4 months when placebo was added. In the study in patients with more aggressive cancer, progression-free survival was 6.7 months when Avastin was added to paclitaxel, topotecan, or pegylated liposomal doxorubicin, compared with 3.4 months when these chemotherapies were used on their own.

In cancer of the cervix the average overall survival was 16.8 months with chemotherapy including Avastin compared with 12.9 months on chemotherapy alone. When the type of chemotherapy was taken into account, there was a tendency for patients given cisplatin-based treatment to live on average about 2 months longer than those given topotecan-based treatment, independently of giving Avastin as part of the treatment regimens.

What is the risk associated with Avastin?

The most common side effects with Avastin are hypertension (high blood pressure), fatigue or asthenia (weakness), diarrhoea and abdominal pain. The most serious side effects are gastrointestinal perforation (hole in the gut), haemorrhage (bleeding) and arterial thromboembolism (blood clots in the arteries). For the full list of all side effects reported with Avastin, see the package leaflet.

Avastin must not be used in people who are hypersensitive (allergic) to bevacizumab or any of the other ingredients, to Chinese hamster ovary cell products or other recombinant antibodies. It must not be given to pregnant women.

Why has Avastin been approved?

The CHMP decided that Avastin'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 Avastin?

A risk management plan has been developed to ensure that Avastin 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 Avastin, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Avastin

The European Commission granted a marketing authorisation valid throughout the European Union for Avastin on 12 January 2005.

The full EPAR for Avastin 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 Avastin, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 05-2016.

Avastin

EMA/353945/2016

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