As reported in JAMA Oncology by Kevin J. Harrington, MBBS, PhD, and colleagues, the phase II CheckMate 714 trial has shown that the addition of ipilimumab to nivolumab did not improve objective response rate as first-line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck with platinum-refractory disease (primary endpoint) or platinum-eligible disease.
Kevin J. Harrington, MBBS, PhD
The double-blind trial included 425 patients who did not receive prior systemic therapy for recurrent or metastatic disease from sites in 21 countries. They were randomly assigned 2:1 between October 2016 and January 2019 to receive nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks or placebo for up to 2 years or until disease progression or unacceptable toxicity. Of 241 patients in the platinum-refractory population, 159 were allocated to the combination and 82 to nivolumab. Of 184 patients in the platinum-eligible population, 123 were allocated to the combination and 61 to nivolumab. The primary endpoints were objective response rate and duration of response on blinded independent central review in the population with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck.
Responses
In the platinum-refractory population, objective response was observed in 21 (13.2%, 95% confidence interval [CI] = 8.4%–19.5%) of 159 patients in the combination group vs 15 (18.3%, 95% CI = 10.6%–28.4%) of 82 in the nivolumab group (odds ratio = 0.68, 95.5% CI = 0.33–1.43, P = .29); complete response was observed in 6 (3.8%) vs 2 (2.4%) patients. Median duration of response was not reached (95% CI = 11.0 months to not reached) in the combination group vs 11.1 months (95% CI = 4.1 months to not reached) in the nivolumab group.
In the platinum-eligible population, objective response was observed in 25 (20.3%, 95% CI = 13.6%–28.5%) of 123 patients in the combination group vs 18 (29.5%, 95% CI = 18.5%–42.6%) of 61 in the nivolumab group. Median duration of response was 27.0 months (95% CI = 11.1 months to not reached) vs 24.6 months (95% CI = 5.5 months to not reached).
KEY POINTS
- Among patients with platinum-refractory disease, objective response rates were 13.2% with the combination vs 18.3% with nivolumab alone.
- Among patients with platinum-eligible disease, objective response rates were 20.3% vs 29.5%.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 15.8% of the combination group vs 14.6% of the nivolumab group in the platinum-refractory population, and in 24.6% vs 13.1% in the platinum-eligible population. Treatment-related serious adverse events of any grade occurred in 8.2% vs 9.8% of patients in the platinum-refractory population and 14.8% vs 4.9% of those in the platinum-eligible population. Treatment-related adverse events led to discontinuation of treatment in 5.1% vs 2.5% of patients in the platinum-refractory population and in 9.8% vs 3.3% of the platinum-eligible population.
The investigators concluded, “The CheckMate 714 randomized clinical trial did not meet its primary endpoint of objective response rate benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in recurrent or metastatic squamous cell carcinoma of the head and neck that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.”
Dr. Harrington, of the Royal Marsden Hospital, The Institute of Cancer Research, London, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit jamanetwork.com.
