Nivolumab Plus Ipilimumab vs Nivolumab Alone for Head and Neck Squamous Cell Carcinoma

In the phase 2 CheckMate 714 trial, nivolumab plus ipilimumab did not demonstrate a clinical benefit over nivolumab alone in the first-line setting for patients with recurrent/metastatic head and neck squamous cell carcinoma.

Previously, nivolumab plus ipilimumab “has shown long-term, durable survival benefit for several cancer types,” wrote Kevin Harrington, MBBS, PhD, Royal Marsden Hospital, London, UK, and coauthors. However, this combination in the first-line setting did not demonstrate a statistically significant improvement in overall survival (OS) when compared with the EXTREME regimen among patients with recurrent/metastatic head and neck squamous cell carcinoma.

This double-blind clinical trial enrolled 425 patients with either platinum-refractory or platinum-eligible recurrent or metastatic head and neck squamous cell carcinoma who had not previously received systemic therapy for recurrent or metastatic disease. Of the total 425 patients, 241 were platinum-refractory and 184 were platinum-eligible. Patients were randomized on a 2-to-1 basis to receive either 3mg/kg nivolumab every 2 weeks plus 1mh/kg ipilimumab every 6 weeks (n = 144) or nivolumab plus placebo (n = 72) for up to 2 years.

The primary end point was objective response rate (ORR) in the platinum-refractory population, along with duration of response (DoR) and time to response (TTR). Secondary end points included ORR and DOR in the platinum-eligible population, and progression-free survival (PFS), and OS in both populations.

The study did not meet the primary end point of ORR in the platinum-refractory population. The ORR in the combination arm was 13.2% vs 18.3 in the nivolumab alone arm (odds ratio [OR], 0.68; 95.5% confidence interval [CI], 0.33 to 1.43; P = .29). The study did not meet the primary end point. The median TTR was 2.6 months in the combination arm vs 1.5 months in the nivolumab alone arm. The DoR was not reached in the combination arm and was 11.1 months in the nivolumab arm. There was also no improvement in PFS or OS seen in the combination arm vs the nivolumab alone arm. There was also no ORR benefit seen in the combination arm vs the nivolumab alone arm in the platinum-eligible population.

Dr Harrington et al concluded, “Nivolumab plus ipilimumab was not associated with clinical benefit in either the population with platinum-refractory [recurrent/metastatic head and neck squamous cell carcinoma] or the population with platinum-eligible [recurrent/metastatic head and neck squamous cell carcinoma],” adding, “the role of dual immunotherapy in the first-line treatment of [recurrent/metastatic head and neck squamous cell carcinoma] remains unclear and needs further investigation.”

Source:

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:1..1001/jamaoncol.2023.0147