Can biological therapies nivolumab and ipilimumab prevent stage IV melanoma from returning?

This study examined if biological therapies nivolumab (Opdivo) and ipilimumab (Yervoy) could safely prevent cancer return in patients with stage IV melanoma that has been surgically removed. The results showed that nivolumab and ipilimumab were effective at preventing recurrence but nivolumab alone was safer for patients.

Biological therapies such as nivolumab and ipilimumab have significantly improved treatment results for patients with melanoma. These therapies work by preventing cancer cells from switching the immune system off. This allows the immune system to be active and to kill cancer cells. 

There is little data about patients with stage IV melanoma with no signs of cancer following surgery. Adjuvant treatment is the use of therapies to prevent a return of cancer (relapse) after initial therapy such as surgery. It is unknown if nivolumab and ipilimumab are useful adjuvant therapies for patients with stage IV melanoma but no signs of cancer after surgery.

167 with stage IV melanoma surgically removed were divided into three groups. All patients had no signs of cancer after surgery. 56 patients received nivolumab plus ipilimumab, 59 patients received nivolumab alone and 52 received a placebo. Patients’ results were recorded for 28.4 months on average.

After 1 year, 75% of the nivolumab plus ipilimumab group, 52% of the nivolumab alone group, and 32% of the placebo group had survived without relapse. After 2 years, 70% of the nivolumab plus ipilimumab group, 42% of the nivolumab alone group, and 14% of the placebo group had survived without relapse.

Patients who received nivolumab plus ipilimumab were 77% more likely to survive without relapse compared to a placebo. Patients who received nivolumab alone were 44% more likely to survive without relapse compared to a placebo. Patients were 60% more likely to survive without relapse with nivolumab plus ipilimumab than with nivolumab alone.

The average length of survival without relapse was not reached for the nivolumab plus ipilimumab group. The average length of survival without relapse was 12.4 months in the nivolumab alone group and 6.4 months for the placebo group.

96% of the nivolumab plus ipilimumab group, 84% of the nivolumab alone group, and 55% of the placebo group experienced side effects. The most common side effect was liver problems in the nivolumab plus ipilimumab group (42%) and fatigue the nivolumab alone (21%) and placebo (26%) groups.

The authors concluded that nivolumab plus ipilimumab combination was very effective as adjuvant therapy for patients with stage IV melanoma that has been surgically removed. Nivolumab alone was safer for these patients.

The manufacturer of nivolumab and ipilimumab, Bristol-Myers Squibb, funded this study.  This study would benefit from including more patients and for a longer duration.