Yervoy

Yervoy (ipilimumab)

On the 25th of March 2011, it was announced that the US Food and Drug Administration (FDA) had approved Yervoy (ipilimumab) for the treatment of patients with inoperable or metastatic melanoma. Yervoy is the first and only approved therapy for metastatic or inoperable melanoma to demonstrate an improvement in overall survival.

Phase 3 Clinical Trial

In a randomised, double-blind Phase 3 study it was found that Yervoy delivers a significant improvement in overall survival in patients with inoperable or metastatic melanoma. The international study of 676 patients with melanoma established the drug’s safety and effectiveness. Patients in the study had received at least one cycle of prior therapy.. The study was designed to measure the overall survival of patients (i.e. the length of time from randomisation to death). Participants either received ipilimumab, an experimental tumour vaccine called gp100 or a combination of both.

The Results

According to the clinical study report, the 1-year and 2-year survival rates were significantly higher in the ipilimumab only and ipilimumab plus gp100 groups. The estimated 1-year survival rate for the ipilimumab only group was 45.6% while the ipilimumab plus gp100 group had an estimated 1-year survival rate of 43.6%. The group which received the gp100 vaccine alone had an estimated 1-year survival of 25.3%. The estimated 2-year survival rates were 23.5%, 21.6% and 13.7% respectively. The study also showed that the results from the ipilimumab treated groups were durable.

Patients treated with ipilimumab demonstrated durable survival benefits compared to those who received gp100. 17.4% of those in the ipilimumab plus gp100 vaccine groups, who achieved an objective response, maintained that response for at least 2 years. 60% of the subjects treated with ipilimumab alone, who achieved an objective response, maintained their response for at least 2 years. Sixty percent of patients who responded to ipilimumab maintained their response for longer than 2 years while none of the subjects treated with gp100 remained in response at the 2-year time point. .

Those patients who received ipilimumab or a combination of the gp100 vaccine and ipilimumab had a median overall survival of 10 months compared to 6 months for those who received the gp100 vaccine alone.

The Drug

Yervoy, which is the product of more than 14 years of research and development, is a monoclonal antibody which is administered intravenously. Once inside the body, Yervoy blocks a molecule known as cytotoxic T-lymphocyte antigen (CTLA-4). CTLA-4 plays a role in either slowing down or turning off the body’s immune system, which in turn reduces its ability to fight and destroy cancer cells. Yervoy appears to work by stimulating the body’s immune system to recognise and attack melanoma cells.

“Late stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient’s life” stated Richard Pazdur, M.D, director of the Office of Oncology Drug Products in the FDA’s Centre for Drug Evaluation and Research. "Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment.

The Side Effects

Common immune-related side effects associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). When severe side effects occurroccur , Yervoy is stopped and corticosteroid treatment is started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.

Due to the unusual and severe side effects associated with Yervoy, the therapy has been approved in the US with a Risk Evaluation and Mitigation Strategy to inform US health care professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy's potential side effects .

For full infomration about side effects refer to the Yervoy website

Yervoy has been developed by Bristol-Myers Squibb (BMS). It is not yet available in New Zealand. Click here to read about how new medicines are approved and funded in New Zealand.

If you have further questions about melanoma and its treatment, we encourage you to talk to your own clinical team.