Ipilimumab With Dacarbazine Improves Survival in Metastatic Melanoma

Malignant melanoma is a serious cancer that arises from pigment cells called melanocytes. Since melanocytes are usually located in the skin, malignant melanomas are usually skin cancers. In rare cases, they may arise from other sites like the eye, ears, digestive tract and vagina. When malignant melanoma spreads to other parts of the body, it is referred to as metastatic melanoma. Patients with metastatic melanoma have a low survival rate. Studies indicate that an ipilimumab which is a novel monoclonal antibody when combined with an anticancer drug dacarbazine may provide benefit in patients with metastatic melanoma. These studies were conducted in small groups of patients.

Ipilimumab is a new monoclonal antibody approved by the FDA in March 2011 for the treatment of metastatic melanoma. It is marketed as Yervoy in the United States. The results of a Phase III study that the drug underwent have been recently published in the New England Journal of Medicine. The study was sponsored by the pharmaceutical giant, Bristol-Myers Squibb and was conducted between August 2006 and January 2008. It compared the effects of ipilimumab or placebo when combined with dacarbazine on survival in 502 patients with previously untreated metastatic melanoma and a life expectancy of 16 weeks or more.

Patients were administered ipilimumab (at a dose of 10 mg/kg) plus dacarbazine or dacarbazine plus placebo at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22.  Neither the patients nor the treating doctors were aware as to which medications the patients received. This was done to avoid any bias in the results. At week 24, patients without any adverse effects during this period were put on either placebo or ipilimumab every 12 weeks until the disease progressed further, the patient developed side effects, or the study ended. The tumor was assessed radiologically as well as by comparing photographs at specific times during the study.

Some patients discontinued the treatment due to disease progression (more in the dacarbazine plus placebo group) or the development of adverse effects (more in the ipilimumab plus dacarbazine group).

The research results found that overall survival was better in the ipilimumab-dacarbazine group. This group however also showed a higher incidence of adverse effects like increase in liver enzymes, diarrhea, itching and rash.

Compared to previous studies, the research found a decrease or absence of certain adverse effects in this study such as digestive tract perforations, hypophysitis (inflammation of the pituitary gland), diarrhea and colitis. However, increase in liver enzymes was higher when compared with previous studies. One reason could be that dacarbazine, which is known to cause liver damage, was also administered to the patients.

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The study thus concluded that a combination of ipilimumab with dacarbazine improves survival when compared to dacarbazine and placebo in patients with previously untreated metastatic melanoma.

Reference:

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1. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C et al. Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. N Engl J Med 2011; 364:2517-2526.

Source-Medindia