NEW ORLEANS — The addition of nivolumab to ipilimumab conferred a statistically significant PFS benefit among treatment-naive patients with BRAF wild-type melanoma, according to updated results of the CheckMate 069 study presented at the American Association for Cancer Research Annual Meeting.
Researchers also reported a higher 2-year OS rate among BRAF wild-type patients assigned the combination.
Michael A. Postow
“[OS] was an exploratory endpoint, so I would caution about making comparisons between these two treatment arms,” Michael A. Postow, MD, medical oncologist with Memorial Sloan Kettering Cancer Center, said during his presentation. “However, both had impressive 1- and 2-year overall survival rates.”
CheckMate 069 a randomized phase 2 trial compared the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) with ipilimumab alone in 142 patients with previously untreated melanoma.
Researchers assigned patients 2:1 to ipilimumab 3 mg/kg plus either nivolumab 1 mg/kg or placebo every 3 weeks for four doses, followed by nivolumab or placebo every 2 weeks until disease progression or unacceptable toxicity.
Investigator-assessed objective response rate (ORR) in patients with BRAF wild-type melanoma served as the primary endpoint. Secondary endpoints included PFS in patients with BRAF wild-type tumors, ORR in patients with BRAF V600 mutations and safety. OS served as an exploratory endpoint.
The majority of study participants (n = 109; 76.7%) were BRAF wild-type; of these, 72 received the combination treatment and 37 received ipilimumab alone.
Initial results published last year in The New England Journal of Medicine showed the combination conferred a statistically significant improvement in ORR (61% vs. 11%; P < .0001) and PFS (median, not reached vs. 4.4 months; HR = 0.4; 95% CI, 0.23-0.68) compared with ipilimumab alone in patients with previously untreated BRAF wild-type melanoma.
At AACR, Postow presented updated efficacy data, as well as the initial OS results.
After minimum follow-up of 2 years, among BRAF wild-type patients, median PFS had not been reached in the combination group but was 4.4 months in the ipilimumab monotherapy group (HR = 0.35; P < .0001). However, the PFS benefit appeared to plateau after 12 months, Postow said.
Median OS among BRAF wild-type patients had not been reached in the combination group but was 24.8 months in the ipilimumab monotherapy group. Researchers reported a higher 2-year OS rate in the combination group (69% vs. 53%).
Responses to the combination remain durable, and median duration of response has not been reached.
Patients assigned the combination were more likely to experience grade 3 or grade 4 treatment-related adverse events (54% vs. 20%) and discontinue treatment due to these events (30% vs. 9%). However, adverse events were consistent with those previously reported, and more than 85% resolved with immune-modulating medication. No additional treatment-related deaths were reported.
“Further information about survival outcomes with this combination will be assessed in the ongoing phase 3 CheckMate 067 study, in which there are three randomized arms: this particular combination, nivolumab monotherapy and ipilimumab monotherapy,” Postow said. “Those data, obviously, are eagerly anticipated.” – by Mark Leiser
Postow M, et al. Abstract CT002. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.
Postow MA, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414428.
Postow reports grant/research support from, advisory roles with or speakers bureau roles with Bristol-Myers Squibb, Caladrius and Merck. Please see the full study for a list of all other researchers’ relevant financial disclosures.