An European Medicines Agency (EMA) panel has recommended the approval of the combination of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb) for the treatment of advanced (unresectable or metastatic) melanoma.
The nivolumab–ipilimumab combination was approved in the United States in 2015.
The recommendation comes from the Committee for Medicinal Products for Human Use (CHMP), which issued a positive opinion on the combination on the basis of data from the phase 3 CheckMate-067 trial and the phase 2 CheckMate-069 trial, with supportive data from the phase 1b CA209-004 study.
The CHMP noted that an increase in progression-free survival for the combination (compared with nivolumab alone) is established only in patients with low tumor PD-L1 expression.
The double-blind CheckMate-067 trial compared the combination with ipilimumab and nivolumab monotherapies in 945 treatment-naïve patients with advanced melanoma, with or without a BRAF V600 mutation.
After a follow-up period of at least 9 months, median progression-free survival was 2.9 months for ipilimumab alone, 6.9 months for nivolumab alone, and 11.5 months for the combination, according to results first reported at the 2015 annual meeting of the American Society of Clinical Oncology.
The risk for progression or death was 58% lower with the combination than with ipilimumab alone (hazard ratio [HR], 0.42; P < .001), and was 43% lower with nivolumab alone than with ipilimumab alone (HR, 0.57; P < .001).
Treatment-related adverse events were much more common in patients treated with the combination than with either monotherapy.
Specifically, grade 3/4 adverse events occurred in 55.0% of the combination group, but in only 16.0% of the nivolumab group and 27.3% of the ipilimumab group.
Among the most common serious adverse events in the combination group were grade 3/4 diarrhea, which occurred in 9.3% of the patients, and similarly high-grade colitis, which occurred in 7.7%.
In the combination group, 36% of patients discontinued treatment because of adverse events.
This CHMP recommendation will be reviewed next by the European Commission, which has the authority to approve medicines for the European Union.