Mechanism of action of Ipilimumab
Anti-CTLA-4 inhibitors
There has recently been a paradigm shift in advanced melanoma management with the development of two new classes of drugs that work in the treatment of melanoma. The two drugs currently in clinical trials are the biggest ever development in the medical management of melanoma.
Ipilimumab or Yervoy is a monoclonal antibody against the CTLA-4 receptor on T cells (white blood cells that fight cancer). By blocking this receptor the T cell remains activated against cancer cells such as melanoma.
Two phase III trials have shown a survival benefit over traditional melanoma treatment in the form of Dacarbazine or a peptide vaccine. The most recent presented at ASCO in June 2011 showed higher survival rates at 1 year (47.3% v’s 36.3%), 2 years (28.5% v’s 17.9%) and at 3 years (20.8% v’s 11.6%). The earlier study showed a median survival of 10 months in the Ipilimumab plus vaccine arm versus 6.4 months in the vaccine only arm. Survival rates were higher in the Ipilimumab arm at 12 months (46% v’s 25%) and at 24 months (24% v’s 14%). Although not a cure, there is a subset of patients with prolonged survival over ten years.
Overall Survival
Kaplan-Meier Analysis of Survival
However like other chemotherapy drugs there are significant side effects, with some treatment related deaths. Side effects include: diarrhoea deranged liver function tests, itching and rash. Although potentially severe, most side effects can now be well controlled with treatment protocols and only 10% of patients ceased treatment.
Ipilimumab or Yervoy has been approved by the FDA in the management of advanced metastatic melanoma. The drug is available to New Zealanders but it is not funded by Pharmac and therefore is very expensive (approx. $250,000 per year). Please talk to our Medical Oncologists about this drug.