KEY TAKEAWAYS
- CheckMate 651 was a clinical trial (phase III) to compare the first-line treatment of nivolumab plus ipilimumab versus EXTREME in patients with R/M SCCHN who had not received prior systemic therapy.
- The study’s primary endpoints were OS in all randomly assigned patients and patients with a CPS ≥ 20 for programmed death-ligand 1. Secondary endpoints included OS in patients with CPS ≥ 1.
- In patients with CPS ≥ 1, nivolumab plus ipilimumab showed a longer median OS than EXTREME. In CPS ≥ 20 patients, the median progression-free survival was shorter for nivolumab plus ipilimumab than EXTREME. However, the objective response rate was similar, and the median duration of response was longer for nivolumab plus ipilimumab.
- Nivolumab plus ipilimumab showed a more favorable safety profile than EXTREME, with a lower incidence of grade 3/4 treatment-related adverse events.
The CheckMate 651 trial compared EXTREME (cetuximab with cisplatin/carboplatin plus fluorouracil six cycles, then cetuximab maintenance) with first-line nivolumab plus ipilimumab in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN; ClinicalTrials.gov identifier: NCT02741570).
Nivolumab with ipilimumab or EXTREME was randomly assigned to patients without prior systemic therapy for R/M SCCHN. In all randomly allocated groups with a programmed death-ligand 1 positive combination score (CPS) 20, overall survival (OS) was the primary end outcome. Progression-free survival, objective response rate, and duration of response were secondary end criteria in all randomly assigned CPS 20 populations. In contrast, overall survival was the primary endpoint in the programmed death-ligand 1 CPS 1 cohort.
Of the 947 patients, 38.3% had a CPS≥ 20 after randomization. The overall and CPS 20 populations showed no statistically significant changes in OS between nivolumab + ipilimumab and EXTREME (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P =.4951). However, those with a CPS 1 had a longer median OS of 15.7 months compared to 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97) than those with a higher CPS. In addition, the median progression-free survival for patients with a CA 125 score of less than 20 was 5.4 months for those treated with nivolumab and ipilimumab and 7.0 months for those treated with EXTREME; the objective response rate was 34.1% versus 36.0%; and the median duration of response was 32.6 versus 7.0 months.
While 70.7% of patients receiving EXTREME experienced treatment-related side events, only 28.2% of those receiving nivolumab + ipilimumab experienced the same. Neither the randomly assigned nor the CPS 20 populations achieved CheckMate 651’s primary endpoint of OS. The safety profile of nivolumab + ipilimumab was improved over that of EXTREME. However, patients with R/M SCCHN still have an unmet need for treatment options.
Source:https://pubmed.ncbi.nlm.nih.gov/36473143/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02741570/
Haddad, R.I., Harrington, K., Tahara, M., Ferris, R.L., Gillison, M., Fayette, J., Daste, A., Koralewski, P., Zurawski, B., Taberna, M., Saba, N.F., Mak, M., Kawecki, A., Girotto, G., Alvarez Avitia, M.A., Even, C., Toledo, J.G.R., Guminski, A., Müller-Richter, U. and Kiyota, N. (2022). 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. Journal of Clinical Oncology. doi:https://doi.org/10.1200/jco.22.00332.
