Compared with nivolumab alone, ipilimumab plus nivolumab does not provide a clinical benefit in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to trial results published in JAMA Oncology.
In this phase 2 trial, there was no improvement in objective response rate (ORR), progression-free survival (PFS), or overall survival (OS) with ipilimumab plus nivolumab.
The trial (CheckMate 714; ClinicalTrials.gov Identifier: NCT02823574) included 425 patients with recurrent or metastatic HNSCC, some of whom had platinum-refractory disease.
The patients were randomly assigned 2:1 to receive ipilimumab (1 mg/kg every 6 weeks) plus nivolumab (3 mg/kg every 2 weeks) or placebo plus nivolumab (3 mg/kg every 2 weeks). Patients were treated until disease progression, unacceptable toxicity, consent withdrawal, or the 2-year mark.
Of the 241 patients with platinum-refractory HNSCC, 159 were assigned to the combination arm, and 82 were assigned to the monotherapy arm. Of the 184 patients with platinum-eligible HNSCC, 123 were assigned to combination therapy, and 61 were assigned to monotherapy. Baseline characteristics were generally balanced across the treatment arms.
The study’s primary endpoint was ORR in the platinum-refractory patients. At the primary database lock (March 8, 2019), the ORR was 13.2% with ipilimumab plus nivolumab and 18.3% with nivolumab alone (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P =.29).
At the OS database lock (April 6, 2020), in patients with platinum-refractory HNSCC, the ORR was 13.2% with the combination and 19.5% with nivolumab alone. In patients with platinum-eligible disease, the ORR was 20.3% with the combination and 29.5% with nivolumab alone.
In patients with platinum-refractory HNSCC, the median duration of response was 26.7 months with ipilimumab plus nivolumab and 11.1 months with nivolumab monotherapy. In patients with platinum-eligible disease, the median duration of response was 27.0 months and 24.6 months, respectively.
The median PFS in platinum-refractory patients was 2.6 months both for the combination and monotherapy (hazard ratio [HR], 1.02; 95% CI, 0.76-1.37). In platinum-eligible patients, the median PFS was 2.8 months and 2.9 months, respectively (HR, 1.07; 95% CI, 0.76-1.52).
The median OS in platinum-refractory patients was 10.0 months with ipilimumab plus nivolumab and 9.6 months with nivolumab alone (HR, 1.08; 95% CI, 0.80-1.46). In platinum-eligible patients, the median OS was 10.0 months and 12.9 months, respectively (HR, 1.15; 95% CI, 0.80-1.65).
Treatment-related adverse events were similar between the treatment arms, the researchers reported.
Based on these results, the researchers concluded that the role of dual immunotherapy for recurrent or metastatic HNSCC “remains unclear and needs further investigation.”
Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Harrington KJ, Ferris RL, Gillison M, et al. Efficacy and safety of nivolumab plus ipilimumab vs nivolumab alone for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck: The phase 2 CheckMate 714 randomized clinical trial. JAMA Oncol. Published online April 6, 2023. doi:10.1001/jamaoncol.2023.0147