Nivolumab/Ipilimumab Does Not Yield Response in Advanced HNSCC

Treatment with first-line nivolumab (Opdivo) plus ipilimumab (Yervoy) did not induce more responses vs nivolumab monotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC), according to findings from the phase 2 CheckMate 714 trial (NCT02823574).

"The role of dual immunotherapy in the first-line treatment of [recurrent or metastatic] HNSCC remains unclear and needs further investigation," the study authors stated.

In patients with platinum-refractory disease, the overall response rate (ORR) was 13.2% (95% CI, 8.4%-19.5%) in the combination arm vs 18.3% (95% CI, 10.6%-28.4%) for patients in the monotherapy arm (odds ratio [OR], 0.68; 95% CI, 0.33-1.43; P = .29). In patients with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) in the nivolumab plus ipilimumab arm vs 29.5% (95% CI, 18.5%-42.6%) in the nivolumab alone arm.

The investigators noted the research should continue to identify patient subgroups that may benefit from treatment with the combination.

“Patient subpopulations that would benefit from nivolumab plus ipilimumab over nivolumab for [recurrent or metastatic] HNSCC are yet to be identified, and further research to identify biomarkers to optimize patient selection and improve patient outcomes is warranted,” the study authors wrote. “The role of dual immunotherapy in the first-line treatment of [recurrent or metastatic] HNSCC remains unclear and needs further investigation.”

The double-blind randomized trial enrolled 425 patients, and the study was conducted between October 2016 and January 2019. Patients were randomized 2:1 to receive 3 mg/kg of nivolumab intravenously every 2 weeks plus 1 mg/kg of intravenous ipilimumab every 6 weeks or matched nivolumab.

A total of 241 patients were included in the platinum-refractory group, with a median age of 59 years. Additionally, 80.5% were male, including 159 in the combination arm and 82 in the monotherapy arm. For patients who were platinum-eligible (n = 184), the median age was 62 years and 82.6% were male. Moreover, 99.2% vs 100.0% received treatment either in the combination or monotherapy arms, respectively.

Patient characteristics were similar between arms, according to investigators. At a minimum follow-up of 9.6 months—the primary database lock—12.0% of patients in the combination arm and 19.5% in the monotherapy arm continued with treatment. With a minimum follow-up of 22.2 months—the overall survival (OS) database lock—no patients in the combination arm and 2 in the monotherapy arm continued treatment. The main reason for discontinuation included disease progression in 71.5% vs 76.8% between each arm, respectively.

In the combination arm, the median time to response was 2.6 months (range, 1.1-6.6) vs 1.5 months (range, 1.2-7.7) in the monotherapy arm, and the median duration of response (DOR) was not reached (NR; 95% CI, 11.0-NR) vs 11.1 months (95% CI, 4.1-NR). Additionally, 90.5% (95% CI, 67.0%-95.7%) of patients in the nivolumab plus ipilimumab arm compared with 66.7% (95% CI, 37.5%-84.6%) in the nivolumab arm had responses that were ongoing for over 6 months.

The OS database lock determined an additional patient in the monotherapy arm responded, leaving investigators with a total ORR of 19.5% (95% CI, 11.6%-29.7%), with 5.0% of patients having a complete response in the combination arm vs 2.4% in the monotherapy arm. In the nivolumab plus ipilimumab arm, the median DOR was 26.7 months (95% CI, 26.7-NR) vs 11.1 months (95% CI, 4.9-NR) in the monotherapy arm. Additionally, 95.2% (95% CI, 70.7%-99.3%) in the combination arm vs 68.8% (95% CI, 40.5%-85.6%) in the monotherapy arm continued to respond for over 6 months.

For patients who were platinum-eligible, the median DOR was 27.0 months (95% CI, 11.1-NR) vs 24.6 months (95% CI, 5.5-NR) with ongoing responses for more than 6 months reported in 91.3% (95% CI, 69.5%-97.8%) vs 76.7% (95% CI, 49.2%-90.6%) of those in combination and monotherapy arms, respectively.

Of note, progression-free survival (PFS) and OS were not improved in the platinum-refractory or platinum-eligible populations.

Investigators also analyzed PD-L1 expression of 1% or more or less than 1% at baseline as well as TIA-GEP score of 10 or more or less than 10. They reported no significant differences in ORR, PFS, or OS by PD-L1 status in either subgroup.

In regard to safety, grade 3/4 adverse effects (AEs) or treatment-related AEs (TRAEs) were similar across both arms. Grade 3/4 serious TEAEs occurred in 5.7% of patients in the combination arm and 3.7% in the monotherapy arm for those in the platinum-refractory population. For patients in the nivolumab plus ipilimumab arm, discontinuation due to high-grade toxicities occurred in 2.5% of patients vs 0.0%.

In the platinum-eligible group, grade 3/4 serious TEAEs occurred in 13.1% vs 3.3% and 8.2% vs 3.3% discontinued treatment in the combination and monotherapy arms, respectively. There were no treatment-related deaths in either population.

Immune-mediated grade 3/4 AEs occurred in 3.2% of patients in the platinum-refractory group and 4.9% in the platinum-eligible group. Additionally, the risk of hepatitis in the monotherapy arm among those with platinum-eligible disease was 3.3%.

Reference

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. April 6, 2023. doi:10.1001/jamaoncol.2023.0147