Ipilimumab (Yervoy) in combination with nivolumab (Opdivo) for the treatment of melanoma

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of ipilimumab (trade name: Yervoy) combined with nivolumab (trade name: Opdivo) for people with advanced melanoma.

The manufacturer provided two ongoing studies that compared ipilimumab plus nivolumab with nivolumab alone as first-line treatment in people without a BRAF V600 mutation. In the larger study, the results of 429 people could be used in the analysis. About half of them received treatment with ipilimumab and nivolumab, while the other half was given nivolumab only. At the time of the analysis, the study had been monitoring the participants for 4 years. The data of 30 people in the smaller study could be used in the analysis.

Both studies involved patients without a BRAF V600 mutation whose cancer had already spread (metastasized) at the time of diagnosis or who could not have surgery. Despite the advanced stage of their condition, the patients were in good general health. The following results were found:

What advantages does the combination of ipilimumab plus nivolumab have?

The combination of ipilimumab plus nivolumab wasn’t found to have any advantages when compared with nivolumab alone.

What disadvantages does the combination of ipilimumab plus nivolumab have?

In terms of serious side effects, the studies suggest that the combination of ipilimumab plus nivolumab has a disadvantage. In the larger study, serious side effects occurred with this drug combination after 2 months on average (median value), and after about 11 months when nivolumab was used alone.

Treatment stopped due to side effects: The studies also suggest that the combination therapy has a disadvantage here: In the larger study, about 46 out of 100 people stopped this treatment due to side effects within 3 years. This only happened in about 14 out of 100 people who received nivolumab alone.

Health-related quality of life (cognitive functioning): The larger study suggests that patients who received ipilimumab plus nivolumab had poorer concentration and memory than people who were given nivolumab alone.

No difference between the treatments was found in other aspects, such as everyday physical or social activities. 

No differences

Life expectancy: In the larger study, 50 to 56 out of 100 people passed away in each group.

General health: There was no difference between the treatments here, either.

There was also no difference regarding the following symptoms:

  • Pain
  • Exhaustion
  • Shortness of breath
  • Sleep problems
  • Loss of appetite
  • Nausea and vomiting
  • Diarrhea

What remains unanswered?

Immune-mediated severe side effects: Immune-mediated side effects are medical conditions in which a person's immune system attacks their own body. The manufacturer didn’t provide any suitable data with which to look into this.

More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of ipilimumab (Yervoy) in combination with nivolumab (Opdivo).

Labels: C43, Ipilimumab, Yervoy