Nivolumab Plus Ipilimumab Did Not Improve OS for Patients With Squamous Cell Carcinoma of the Head and Neck

The CheckMate 651 trial found first-line nivolumab plus ipilimumab did not improve the overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), compared to the EXTREME regimen (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ 6 cycles followed by cetuximab maintenance).

As Robert Haddad, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues wrote, “there persists an unmet need to improve clinical outcomes” in this patient population.

Gary K Schwartz, MD, associate editor of Journal of Clinical Oncology, added, “Use of immunotherapy in the treatment of SCCHN is still evolving, with a continued unmet need for first-line regimens that provide durable clinical benefit with tolerable safety.”

In this open-label, phase 3 trial, 947 patients with recurrent or metastatic SCCHN who had not had any prior systemic treatment were randomly assigned on a 1-to-1 basis to receive either nivolumab plus ipilimumab (n = 472), or EXTREME (n = 475). In the nivolumab-ipilimumab arm 39.2% had PD-L1 combined positive score (CPS) ≥ 20, compared with 37.5% in the EXTREME arm. The primary end points of this study were overall survival in all randomly assigned and CPS ≥ 20 populations.

At the data cutoff date of June 21, 2021, the median follow-up duration was 39.1 months. In the nivolumab-ipilimumab arm no patients were remaining on treatment, with 8.5% completing the full 2-year course. In the EXTREME arm, 1.6% of patients remained on treatment. The median OS of the nivolumab-ipilimumab arm was 13.9 months, compared with 13.5 months in the EXTREME arm. The median OS of the CPS ≥ 20 population in the nivolumab-ipilimumab arm was 17.6 months compared to 14.6 months in the CPS ≥ 2o population in the EXTREME arm. The primary end points of OS in the nivolumab-ipilimumab vs EXTREME arms were not met for either all randomly assigned population (hazard ratio [HR], 0.95; 97.9% confidence interval [CI], 0.80 to 1.13; P = .4951), or CPS ≥ 20 populations (HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469).

Grade 3/4 treatment-related adverse events were reported in 28.2% of the nivolumab-ipilimumab arm and 70.7% of the EXTREME arm. In the nivolumab-ipilimumab arm, 1.3% of treatment-related deaths were reported, compared with 1.8% in the EXTREME arm.

Dr Haddad et al concluded, “First-line nivolumab plus ipilimumab did not result in a statistically significant improvement in OS versus EXTREME in platinum-eligible [recurrent/metastatic] SCCHN in the all randomly assigned or CPS ≥ 20 populations. Safety with nivolumab plus ipilimumab was favorable compared with EXTREME.”

Source:

Haddad RI, Harrington K, Tahara M, et al. Nivolumab plus ipilimumab versus EXTREME regimen as first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck: The final results of CheckMate 651. J Clin Oncol. Published online December 6, 2022. doi:10.1200/JCO.22.003322