Ipilimumab improves long-term survival in advanced melanoma

Ipilimumab, a fully human monoclonal antibody, has been shown to improve long-term survival in previously treated patients with advanced melanoma.

The agent extended the survival of such patients by 34 percent when compared with the gp100 vaccine, an experimental melanoma peptide vaccine which has previously shown modest anti-cancer activity and superiority to interleukin-2, alone and in combination. [NEJM 2010; 2010 Jun 5. Epub ahead of print]

These results, from a large-scale, randomized, phase III clinical trial, represent the first time a drug has been shown to prolong survival in this setting, where few treatment options exist.

“Over the last 30 years, randomized clinical trials have repeatedly failed to demonstrate an improvement in overall survival in patients with advanced melanoma. It’s an extremely difficult disease to treat,” said lead researcher Dr. Steven O’Day, chief of research and director of the melanoma program at The Angeles Clinic and Research Institute in Los Angeles, California, US, and clinical associate professor of medicine at the University of Southern California Keck School of Medicine. “These results are an exciting advance, both for patients with advanced melanoma and for the field of cancer immunology.”

In the study, conducted at 125 centers worldwide, a total of 676 patients with advanced stage III or IV melanoma were randomized to receive double-blind treatment with either ipilimumab alone (N=137), ipilimumab in combination with the gp100 vaccine (N=403), or gp100 vaccine alone (N=136). In those receiving ipilimumab, a dosage of 3 mg/kg was given every 3 weeks for 12 weeks.

The median overall survival of patients receiving ipilimumab alone was 10.1 months, compared with a median of 6.4 months for those receiving gp100 vaccine monotherapy (hazard ratio for death, 0.66; P=0.003). Patients receiving ipilimumab in combination with gp100 vaccine also lived for a significantly longer median duration (10.0 months) than those receiving gp100 vaccine alone (6.4 months; hazard ratio for death, 0.68, P<0.001).

Two-year survival rates in the ipilimumab monotherapy and combination groups were 24 percent and 22 percent, respectively, compared with only 14 percent in the gp100 vaccine monotherapy group. “Surprisingly the addition of the gp100 vaccine … in this trial did not improve survival,” said O’Day.

In terms of safety, ipilimumab was generally well tolerated. O’Day commented that the majority of adverse events were “immune-related” and mostly mild-to-moderate and reversible. However, 10 to 15 percent of recipients experienced serious adverse events (such as colitis) requiring steroid treatment, compared with only 3 percent of those receiving the gp100 vaccine alone.

Source: mims.com