Treatment with nivolumab and ipilimumab in patients with advanced melanoma produced significantly higher rates of response and progression-free survival compared with ipilimumab alone.
Combined treatment with the T-cell checkpoint pathway inhibitors nivolumab and ipilimumab produced significantly higher rates of response and progression-free survival among patients with advanced melanoma (regardless of BRAF mutation status) than did treatment with ipilimumab alone, according to the phase I results of a trial published in the New England Journal of Medicine and presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting.
“On the basis of the high degree of tumor reduction in the current study, with a high rate of complete responses, a favorable clinical benefit can be anticipated with longer follow-up,” wrote study author F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute, and colleagues.
The phase I dose-escalation study included 142 patients with treatment-naive metastatic melanoma. Patients were randomly assigned 2:1 to ipilimumab 3 mg/kg with nivolumab 1 mg/kg or placebo every 3 weeks for four doses, followed by nivolumab 3 mg/kg or placebo every 2 weeks.
In patients with BRAF wild-type tumors, combined treatment resulted in an objective response rate of 61% compared with 11% in those assigned ipilimumab alone (P < .001). Complete responses occurred in 22% of patients assigned to the combined immunotherapy treatment and none of the patients assigned to monotherapy.
Patients with BRAF-positive disease assigned to the combination therapy had an objective response rate of 52%, with 22% of patients achieving a complete response.
“In the combination group, the objective response rate was independent of tumor PD-L1 status: 58% (95% CI, 37 to 78) among patients with PD-L1–positive tumors and 55% (95% CI, 41 to 69) among patients with PD-L1–negative tumors,” the researchers wrote. “In the ipilimumab-monotherapy group, a numerically higher objective response rate was observed among patients with PD-L1–positive tumors than among patients with PD-L1–negative tumors (18% [95% CI, 2 to 52] vs 4% [95% CI, 0 to 19]).”
Additionally, patients assigned to combination therapy did not yet reach a median progression-free survival compared with 4.4 months for ipilimumab monotherapy. The median progression-free survival for combined treatment in BRAF-positive patients was 8.5 months compared with 2.7 months in the monotherapy group.
“In general, the spectrum of select adverse events that we observed was consistent with previous experience with the combination therapy,” the researchers wrote. “Three deaths related to the combination regimen were reported in this study; these deaths could be linked to preexisting conditions that were related to the cause of death or that required medical procedures that might have contributed to the death.”
Combined treatment was associated with a higher rate of drug-related grade 3 or 4 adverse events than was monotherapy (54% vs 24%).