Monday August 22 2011
Yervoy is approved for late-stage skin cancer only
A new skin cancer drug has been approved for use in Europe, several newspapers have reported today. The drug, called ipilimumab (brand name Yervoy), has been dubbed a “wonder drug for skin cancer” on the front page of the Daily Express. The Daily Mail calls it the “first real advance” in skin cancer treatment since the 1970s.
Newspapers have given varying estimates of how much the drug will cost. The Daily Mail says it will cost £18,000 per course, while The Daily Telegraph puts the total cost at around £75,000 per patient.
Why is the drug in the news now?
The drug ipilimumab has just been granted ‘marketing authorisation’ by the European Commission, meaning that the drug can be sold throughout the European Union. The European Commission has made this decision based on the advice of The European Medicines Agency (EMA), which has the role of reviewing the evidence regarding the efficacy and safety of drugs and advising on whether it thinks a drug should be allowed to be sold in the EU. This licence only covers the use of the drug in the specific circumstances for which evidence has been submitted. The drug has not been approved for treating all forms or stages of skin cancer.
What is Yervoy used for?
Yervoy has been granted a licence for use to treat adults with advanced melanoma skin cancer who have received treatment that has not worked or has stopped working.
Advanced melanoma is the term usually used to describe stage III and stage IV cancers. In stage III, the cancer has spread to lymph nodes. Stage III is subdivided into three further stages depending on the number and size of lymph nodes involved and whether or not the primary melanoma has ulcerated. In stage IV, the cancer has spread to other organs in the body. The term ‘advanced melanoma skin cancer’ does not necessarily imply that the person has already received treatment that has failed. This is because a person may present to their doctors at this stage if the cancer has not been detected earlier.
The licence for Yervoy only covers the use of the drug in people with advanced melanoma that has already been treated. It does not cover use of the drug in any other way. Therefore it does not cover use of the drug as a first treatment for people with advanced melanoma skin cancer – i.e. people who have been initially diagnosed in stage III or IV and have not yet received other treatments. This is because the European Medicines Agency has only reviewed evidence on the drug as a second, or subsequent, line of treatment in those with advanced melanoma skin cancer.
Advanced melanoma skin cancer has a poor prognosis. Conventional treatments for stage IV cancers typically involve chemotherapy or radiotherapy to control symptoms, or a type of immunotherapy (often using a drug called interferon). People who have earlier stage III tumours are often treated with surgical removal of the lymph nodes, followed by chemotherapy or immunotherapy.
What is Yervoy and how is it used?
Yervoy is what is known as a “monoclonal antibody”: antibodies are types of proteins that help the immune system identify and fight threats. ‘Monoclonal’ means that the drug contains just one type of antibody targeted against a specific protein. Yervoy targets a protein found on the surface of one type of immune system cell (T-cells). The drug is thought to act by making the immune system mount a prolonged attack on the cancer cells.
The drug is given intravenously over a 90-minute period, at a dose of 3mg per kg of body weight. The patient receives four doses of the drug with three weeks between each dose. Due to the risk of adverse effects, the patient needs to be monitored before they start the drug in order to detect any liver or thyroid problems, and then monitored regularly during treatment.
On what evidence was the approval based?
The main study of Yervoy in humans evaluated by the EMA was a randomised controlled trial in 676 patients who had already received treatment for advanced melanoma. The patients were treated with Yervoy, another new drug called gp100, or a combination of Yervoy and gp100. The study found that patients taking Yervoy (either with or without gp100) lived for 10 months on average (median), compared with six months on average with gp100 alone.
One year after treatment began, 46% of people treated with Yervoy were alive compared with 25% of people treated with gp100. At two years, 24% of people treated with Yervoy were alive, compared with 14% of people treated with gp100.
The approval process also considered side effects associated with Yervoy. In this trial, the side effects associated with Yervoy included inflammation and other immune system reactions. The most common side effects, which affected more than 10% of people who took it, were diarrhoea, rash, itching, fatigue, nausea, vomiting, decreased appetite and stomach ache.
The EMA decided that the evidence showed that Yervoy improved overall survival in patients with advanced melanoma whose initial cancer treatment had not worked or had stopped working. These patients usually have low overall survival. The EMA decided that in this specific group of patients the benefits of the drug were greater than its risks.
What happens now?
As the drug has been approved for use in the EU, the drug is likely to be granted a specific licence for use in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA).
The EMA only decides whether the drug is safe and effective enough for use. It does not look at whether the drug provides good “value for money”. The National Institute for Health and Clinical Evidence (NICE) reviews the evidence on a drug to determine how effective and safe it is compared to currently used alternatives, and whether it provides sufficient value for money to be purchased for the NHS in England and Wales. NICE is in the process of evaluating ipilimumab for use in previously treated malignant melanoma where the tumours are not amenable to removal by surgery. Their guidance is expected to be issued in February 2012.
Prior to this, Primary Care Trusts will have to make their own decisions about whether or not to fund provision of the drug. The Daily Mail reports that some regions have decided that the drug will be made available via the Cancer Drugs Fund in the meantime.