Ipilumumab after surgery in high-risk stage III melanoma

The authors aimed to assess the effect of ipilimumab (Yervoy) as an additional therapy after surgery in advanced (stage III) melanoma patients who were at a high risk of relapse.

In the advanced stage of melanoma (stage III), cancer spreads from the skin to nearby lymph nodes (tiny, bean-shaped organs that help fight infections). When melanoma thickness (how far the cancer reaches into the skin) is > 1 mm, the chance of the cancer returning is very high even after complete removal of cancerous lymph nodes. The approved adjuvant (additional) treatment in stage III melanoma after surgery is interferon. This drug, however, has not reduced the chance of relapse significantly in these patients at high risk of recurrence. 

Ipilimumab is an approved drug for the treatment of advanced melanoma, but it has not yet been studied in this adjuvant setting.  

The effectiveness of ipilimumab as therapy following surgery in advanced melanoma was analyzed in the current study.

In this phase 3 clinical trial, 951 melanoma patients.  All patients had previously undergone surgery to remove the cancerous lymph nodes and were thought to be at a high risk of recurrence. Patients were randomly assigned to receive either ipilimumab or placebo (a substance that has no therapeutic effect) and followed for an average of 3 years. 

The average recurrence-free survival (time of survival without return of cancer) was 26.1 months in ipilimumab group compared to 17.1 months in placebo. Patients in the ipilimumab group had 25% reduced risk of reappearance of melanoma compared to placebo. Overall, 46.5% in ipilimumab group versus 34.8% in placebo experienced recurrence-free survival.

Some severe side effects associated with the immune system were reported in the ipilimumab group. They were gastrointestinal disorders (16%), liver problems (11%) and disorders of the endocrine system (related to glands producing hormones; 8%). About 52% of patients in ipilimumab group discontinued treatment due to unfavorable side effects. 1% of patients in the ipilimumab group died due to reasons believed to be drug-related.

The authors concluded that recurrence-free survival was improved by the use ipilimumab as an adjuvant therapy in high-risk melanoma patients after complete surgical removal of tumors.

The severity of ipilimumab -related adverse events is a matter of concern. About 40% of patients discontinued the therapy during the initial treatment period. It remains to be seen whether this effect is due to longer exposure to the drug in the body or greater sensitivity to the drug in stage III melanoma.