NEW YORK (Reuters Health) - Three-year survival rates with advanced melanoma are 52% with nivolumab and 34% with ipilimumab, but 58% with a sequential combination of the two, according to the latest results comparing the two anticancer biologics separately and together.
Median overall survival with a minimum follow-up of 36 months hadn't been reached in the combination group by the data cutoff point. However, it was 37.6 months with nivolumab alone and 19.9 months with ipilimumab alone (P<0.001).
However, combination therapy more than doubled the rate of serious side effects.
"Survival outcomes with either nivolumab-containing regimen were superior to those with ipilimumab alone," according to the team led by Dr. Jedd Wolchok of the Memorial Sloan Kettering Cancer Center in New York.
The latest findings from the CheckMate 067 study, funded by Bristol-Myers Squibb, were released Monday at the European Society for Medical Oncology Congress in Madrid, Spain, and online by the New England Journal of Medicine.
When given as single drugs, the ipilimumab dose was 3 mg/kg every 3 weeks for four doses, and the nivolumab dose was 3 mg/kg every 2 weeks. The double-drug combination started with 1 mg/kg of nivolumab and 3 mg/kg of ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab alone every 2 weeks.
All 945 randomized participants had previously untreated advanced melanoma. Treatment continued until disease progression or the development of unacceptable side effects.
The rates of complete response were 5% with ipilimumab, 16% with nivolumab, and 19% with the combination.
"The two nivolumab-containing groups had significantly longer survival than the ipilimumab group," said the research team. "The rate of overall survival at 2 years was 64% in the nivolumab-plus-ipilimumab group and 59% in the nivolumab group, as compared with 45% in the ipilimumab group."
Patients without BRAF mutations consistently showed lower rates of overall survival and in those participants, adding ipilimumab to nivolumab did not yield a survival advantage over nivolumab alone.
Only when the tumor had a BRAF mutation did the drug combination offer the highest benefit over nivolumab. The 3-year rates of overall survival for those patients were 68% with both drugs, 56% with nivolumab alone, and 37% with ipilimumab alone.
Rates of grade 3 or 4 side effects were 59% with combination therapy, 21% with nivolumab, and 28% with ipilimumab. The most common serious side effects were gastrointestinal, seen in 15%, 4% and 12%, respectively. Skin-related side effects of any severity were the most common: 62% in the combination group, 46% with nivolumab, and 56% among ipilimumab recipients.
Four deaths were considered to be linked to one of the drugs: one from neutropenia (in the nivolumab group), one from colon perforation (in an ipilimumab recipient), and one case each of fatal liver necrosis and the combination of cardiac insufficiency and autoimmune myocarditis (in patients receiving combination therapy).
"The types and frequencies of events were consistent with previous results, and no new types of events occurred," said the Wolchok team. "Most immune-mediated adverse events resolved within 3 to 4 weeks when well-established safety guidelines" were followed.
N Engl J Med 2017.
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