番茄社区

CHICAGO -- High-risk melanoma patients have a reduced level of relapse if they are taking the monoclonal antibody ipilimumab (Yervoy) when compared with placebo, researchers said here.

The 2-year relative risk reduction of experiencing a relapse was 25% compared with placebo, said director general of the Gustave Roussy Cancer Campus Grand Paris in France. In the European Organization for Research and Treatment in Cancer (EORTC) 18071 study, 234 patients out of 475 on ipilimumab had relapsed at 2 years compared with 294 patients out of 476 on placebo, which translated to a median relapse-free survival of 26.1 months compared with 17.1 months for patients assigned to placebo (P=0.0013), he said.

"This study met its primary endpoint of a significant improvement in relapse-free survival with 10 mg/kg ipilimumab versus placebo," Eggermont reported at a press briefing at the annual meeting of the American Society of Clinical Oncology.

However, Eggermont reported that treatment with ipilimumab came with a cost in adverse events. About 2.5% of patients experienced grade 3 or grade 4 toxicities, but five patients died during the trial -- 1.1% of the patients -- from causes attributed to the drug. Three patients died of colitis, one patient died from myocarditis, and one person died from Guillain-Barre syndrome.

Thus, enthusiasm for the treatment was tempered by those fatalities.

"These are toxic drugs," said instructor in medicine at Harvard Medical School/Massachusetts General Hospital, Boston. "I would not use ipilimumab in the adjuvant setting until after we determine overall survival figures." He said that for patients at high risk of relapse he would prefer observation, treatment with interferon, or participation in a clinical trial. "The 25% reduction in relapse seen in this trial is similar or worse than we have seen with interferon."

He told 番茄社区 that "treatment with ipilimumab has a risk of dying. Until we can see the overall mortality rates with this agent so we can compare risks and benefits, I would not use it in the adjuvant setting."

Eggermont said data on overall survival was expected to be ready at subsequent international cancer meetings.

Eggermont and colleagues enrolled patients with stage IIIA melanoma who had undergone complete resection of the cancer and treated the patients in an adjuvant fashion in hopes of reducing relapse. The impact of ipilimumab continued out to 3 years, Eggermont said, noting that 46.5% of ipilimumab patients were relapse-free compared with 34.7% of those on placebo.

"This is a promising treatment -- we saw substantially fewer recurrences among patients who are at high risk of relapse," said Eggermont. "We've seen many impressive new treatments for advanced melanoma in recent years. This trial with ipilimumab is the first to show we may be able to give these new drugs earlier in the course of disease, where they can do more good and potentially cure more patients."

The immunotherapy drug ipilimumab is FDA-approved for the treatment of inoperable stage metastatic melanoma.

High-dose interferon alpha2b and pegylated interferon-alpha2b are approved by the FDA as a post-surgery treatment for patients with stage III melanoma who are at a high risk of relapse.

In Eggermont's study, many of the 951 patients with surgically treated stage III cutaneous melanoma had evidence of spread to lymph nodes. Ipilimumab was given every 3 weeks for four doses, and the treatment continued at 3-month intervals for up to 3 years.

"This study shows that ipilimumab shows activity in the adjuvant setting," said , director of the Los Angeles Skin Cancer Institute at the Beverly Hills Cancer Center, "but the delay of about 10% a year is similar to what we see with other drugs. I think it is very important that we see the overall survival with this study as well as its direct comparison with interferon before we come to determine the role of ipilimumab in the adjuvant setting."