Vectibix

panitumumab

This document is a summary of the European Public Assessment Report (EPAR) for Vectibix. 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 Vectibix.

What is Vectibix?

Vectibix is a concentrate that is made up into a solution for infusion (drip into a vein). It contains the active substance panitumumab.

What is Vectibix used for?

Vectibix is used to treat metastatic cancer of the colon or rectum. This is cancer of the large intestine (bowel) that has spread to other parts of the body. Vectibix is used in patients whose tumour cells contain a non-mutated (wild-type) ‘KRAS’. KRAS is a gene that, when mutated in tumour cells, stimulates tumour growth. Vectibix is used:

• in combination with ‘FOLFOX’ chemotherapy (oxaliplatin, 5-fluorouracil and folinic acid) as first-line treatment (patients who have not been treated before);
• in combination with ‘FOLFIRI’ chemotherapy (irinotecan, 5-fluorouracil and folinic acid) in patients who have already received fluoropyrimidine-based chemotherapy (excluding irinotecan);
• on its own after treatment has stopped working with combinations of anticancer medicines that include a ‘fluoropyrimidine’ (such as 5-fluorouracil), oxaliplatin and irinotecan.

The medicine can only be obtained with a prescription.

How is Vectibix used?

Treatment with Vectibix should be supervised by a doctor who has experience in the use of anticancer therapy. It should only be started after the presence of wild-type KRAS has been confirmed by an experienced laboratory using a validated test method.

The recommended dose of Vectibix is 6 mg per kilogram body weight given once every two weeks as an infusion. The recommended infusion time is around 60 minutes, but larger doses may need 90 minutes. The dose may need to be modified if severe skin reactions occur.

How does Vectibix work?

The active substance in Vectibix, panitumumab, 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. Panitumumab has been designed to attach to EGFR, which can be found on the surface of certain cells, including cells in some tumours. As a result, these tumour cells can no longer receive the messages transmitted via EGFR that they need for growth, progression and spreading (metastasis).

Panitumumab does not seem to work in tumour cells that contain mutated KRAS. This is because their growth is not controlled by signals transmitted via EGFR and they continue to grow even when the EGFR is blocked.

How has Vectibix been studied?

Vectibix has been studied in three main studies. The first involved a total of 463 patients with metastatic cancer of the colon or rectum whose disease had got worse during or after previous treatment that included a fluoropyrimidine, oxaliplatin and irinotecan. The effects of Vectibix in addition to ‘best supportive care’ were compared with those of best supportive care alone. Best supportive care is any medicines or techniques to help patients, such as antibiotics, painkillers, transfusions and surgery, but not other anticancer medicines. The main measure of effectiveness was progression-free survival (how long the patients lived without their disease getting worse). The results of the study were analysed separately in 243 patients whose tumours contained wild-type KRAS and in 184 patients in whom the KRAS gene contained a mutation.

The second main study involved 1,183 patients with metastatic cancer of the colon or rectum who had not been treated before for their metastatic cancer. Vectibix in combination with FOLFOX chemotherapy was compared with chemotherapy alone. The main measure of effectiveness was progression-free survival.

The third main study involved 1,186 patients with metastatic cancer of the colon or rectum who had been treated before. It compared Vectibix in combination with FOLFIRI chemotherapy with chemotherapy alone. The main measures of effectiveness were progression-free survival and overall survival (the length of time the patients lived).

What benefit has Vectibix shown during the studies?

The patients with wild-type KRAS in their tumours who received Vectibix in addition to best supportive care lived for an average of 12.3 weeks without their disease getting worse. This compared with 7.3 weeks in those who received best supportive care alone. In contrast, there was no effect of Vectibix in the patients with mutated KRAS in their tumours, with both groups of patients living for an average of around 7.3 weeks without their disease getting worse.

In the second study, patients with wild-type KRAS receiving Vectibix in combination with FOLFOX lived for 10 months without the disease getting worse compared with 8.6 months for patients receiving FOLFOX alone.

In the third study, patients with wild-type KRAS receiving Vectibix in combination with FOLFIRI lived for 14.5 months compared with 12.5 months in patients receiving FOLFIRI alone. Patients receiving Vectibix also had a longer period of time without their disease getting worse: 6.7 months versus 4.9 months.

What is the risk associated with Vectibix?

In studies, 93% of the patients receiving Vectibix had side effects affecting the skin, although most of these were mild or moderate. The most common side effects with Vectibix (seen in more than 1 patient in 10) are anaemia (low red blood cell counts), conjunctivitis (inflammation of the membrane that lines the front of the eye and the inside of the eyelids), acneiform dermatitis (skin inflammation resembling acne), rash, exfoliative rash (flaky rash), erythema (reddening of the skin), skin exfoliation (skin flaking), pruritus (itching), dry skin, skin fissures (cracks in the skin), diarrhoea, nausea (feeling sick), vomiting, abdominal pain (stomach ache), stomatitis (inflammation of the lining of the mouth ), constipation, fatigue (tiredness), pyrexia (fever), asthenia (weakness), mucosal inflammation (inflammation of the moist body surfaces ), peripheral oedema (swelling, especially of the ankles and feet ), paronychia (nail bed infection), weight loss, hypokalaemia (low blood potassium levels), loss of appetite, back pain, insomnia (difficulty sleeping), dyspnoea (difficulty breathing), cough, nail disorders, alopecia (hair loss) and hypomagnesaemia (low blood magnesium levels). For the full list of all side effects reported with Vectibix, see the package leaflet.

Vectibix must not be used in patients who have had a severe or life-threatening hypersensitivity (allergic) reaction to panitumumab or any of the other ingredients in the past. It must not be used in patients with interstitial pneumonitis or pulmonary fibrosis (lung diseases). Vectibix must not be used with oxaliplatin-containing chemotherapy in patients whose tumour has not been confirmed to contain the non-mutated KRAS gene.

Why has Vectibix been approved?

The CHMP concluded that Vectibix’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Vectibix has been given ‘conditional approval’. This means that there is more evidence to come about the medicine, in particular its safety and effectiveness in patients whose tumours contain wild-type KRAS. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Vectibix?

The company that makes Vectibix will supply the results of additional studies looking at the safety and effectiveness of the medicine in patients with colorectal cancer. These include a study looking at the use of Vectibix in combination with other medicines in patients whose disease has been treated before, as well as a study to confirm the effectiveness of Vectibix, given on its own, in its approved use.

The company will also collect information to check that patients are adequately tested for KRAS mutations.

What measures are being taken to ensure the safe use of Vectibix?

The company that markets Vectibix will ensure that all doctors who are expected to prescribe Vectibix are provided with educational material informing them of the importance of carrying out a KRAS test before treatment with Vectibix and only using Vectibix in patients whose tumour is confirmed to contain the wild-type KRAS gene.

Other information about Vectibix

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Vectibix on 3 December 2007. The conditional marketing authorisation has been renewed every year since then.

For more information about treatment with Vectibix, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This EPAR was last updated on 09/12/2011 .

More detail is available in the Summary of Product Characteristics

Product details

Publication details

Product information

10/11/2011  Vectibix -EMEA/H/C/000741 -II/0017

Contents

• Annex I - Summary of product Characteristics
• Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release
• Annex IIB - Conditions of the Marketing Authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package Leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmaco-therapeutic Group

Antineoplastic agents

Therapeutic Indication

Vectibix is indicated for the treatment of patients with wild-type KRAS metastatic colorectal cancer (mCRC):

• in first-line in combination with FOLFOX
• in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
• as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

Changes since initial authorisation of medicine

Initial Marketing authorisation documents