ESMO 2018: CheckMate 067: 4-Year Follow-up of Nivolumab Plus Ipilimumab in Advanced Melanoma
As reported in The Lancet Oncology and at the European Society for Medical Oncology 2018 Congress by Hodi et al, the 4-year follow-up of the phase III CheckMate 067 trial has shown a continued overall survival benefit with first-line nivolumab (Opdivo) plus ipilimumab (Yervoy) or nivolumab alone vs ipilimumab alone in patients with advanced melanoma. The primary results from the trial showed significant improvements in objective response, progression-free survival, and overall survival with nivolumab plus ipilimumab or nivolumab alone vs ipilimumab alone.
In the trial, 945 patients with unresectable stage III or IV melanoma were randomly assigned to receive nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for 4 doses followed by nivolumab at 3 mg/kg every 2 weeks (n = 314), nivolumab at 3 mg/kg every 2 weeks plus placebo (n = 316), or ipilimumab at 3 mg/kg every 3 weeks for 4 doses plus placebo (n = 315). The coprimary endpoints were progression-free survival and overall survival.
Survival Results
At a minimum follow-up of 48 months, median overall survival was not reached in the nivolumab-plus-ipilimumab group (hazard ratio [HR] = 0.54, P < .0001, vs ipilimumab), 36.9 months in the nivolumab-alone group (HR = 0.65, P < .0001, vs ipilimumab), and 19.9 months in the ipilimumab-alone group. Median progression-free survival was 11.5 months in the combination group (HR = 0.42, P < .0001, vs ipilimumab), 6.9 months in the nivolumab-alone group (HR = 0.53, P < .0001, vs ipilimumab), and 2.9 months in the ipilimumab-alone group.
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 59% of the combination group, 22% of the nivolumab group, and 28% of the ipilimumab group. The most common treatment-related grade 3 adverse events were diarrhea in the combination group (9%) and in the nivolumab group (3%) and colitis in the ipilimumab group (7%); the most common grade 4 adverse event in all three groups was increased lipase (5%, 3%, and 1%, respectively).
A total of 4 treatment-related deaths have occurred during the study, consisting of 2 in the combination group (due to cardiomyopathy and liver necrosis), 1 in the nivolumab group (due to neutropenia), and 1 in the ipilimumab group (due to colon perforation). No treatment-related deaths were observed between the 3-year analysis and the current analysis.
The investigators concluded, “The results of this analysis at 4 years of follow-up show that a durable, sustained survival benefit can be achieved with first-line nivolumab plus ipilimumab or nivolumab alone in patients with advanced melanoma.”
The study was funded by Bristol-Myers Squibb.
Frank Stephen Hodi, MD, of the Dana-Farber Cancer Institute, is the corresponding author for The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
