The final results of the phase III CheckMate 651 trial showed no significant overall survival benefit with first-line nivolumab/ipilimumab vs the EXTREME regimen (cetuximab plus cisplatin or carboplatin plus fluorouracil for up to six cycles, followed by cetuximab maintenance) in recurrent or metastatic squamous cell carcinoma of the head and neck. As reported in the Journal of Clinical Oncology by Robert I. Haddad, MD, and colleagues, these findings were shown among all patients or among those with a PD-L1 combined positive score ≥ 20.
Study Details
In the open-label trial, 947 patients were randomly assigned to receive nivolumab/ipilimumab (n = 472) or EXTREME (n = 475). CPS was < 1 in 92 vs 86 patients, ≥ 1 in 355 vs 372, and ≥ 20 in 185 vs 178. The primary endpoints were overall survival in all randomly assigned patients and in those with a CPS of ≥ 20.
Robert I. Haddad, MD
Key Findings
At database lock (in June 2021), minimum and median follow-up were 27.3 and 39.1 months, respectively.
Among all randomly assigned patients, median overall survival was 13.9 months (95% confidence interval [CI] = 12.1–15.8 months) in the nivolumab/ipilimumab group vs 13.5 months (95% CI = 12.6–15.2 months) in the EXTREME group (hazard ratio [HR] = 0.95, 97.9% CI = 0.80–1.13, P = .4951). Among patients with a CPS ≥ 20, median overall survival was 17.6 months (95% CI = 13.8–22.0 months) in the nivolumab/ipilimumab group vs 14.6 months (95% CI = 12.3–16.0 months) in the EXTREME group (HR = 0.78, 97.51% CI = 0.59–1.03, P = .0469).
With regard to secondary endpoints, among patients with a CPS ≥ 1, median overall survival was 15.7 months (95% CI = 13.7–18.8 months) with nivolumab/ipilimumab vs 13.2 months (95% CI = 11.1–14.6 months) with EXTREME (HR = 0.82, 95% CI = 0.69–0.97). Among patients with a CPS ≥ 20, median progression-free survival was 5.4 months vs 7.0 months (HR = 1.02, 95% CI = 0.78–1.33), objective response rates were 34.1% vs 36.0%, and median duration of response was 32.6 vs 7.0 months.
Subsequent immunotherapy was received by 46% of patients in the EXTREME group vs 9% of the nivolumab/ipilimumab group. In an ad hoc analysis adjusting for potential impact on overall survival, median overall survival was 12.4 months with nivolumab/ipilimumab vs 10.8 months with EXTREME (HR = 0.80, 95% CI = 0.68–0.92) among all randomly assigned patients and 14.1 vs 11.7 months (HR = 0.71, 95% CI = 0.55–0.91) among those with a CPS ≥ 20.
Grade 3 or 4 treatment-related adverse events occurred in 28.2% of patients in the nivolumab/ipilimumab group vs 70.7% of the EXTREME group.
The investigators concluded, “CheckMate 651 did not meet its primary endpoints of overall survival in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.”
Dr. Haddad, of the Division of Head and Neck Oncology, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb in collaboration with Ono Pharmaceutical Company Ltd. For full disclosures of the study authors, visit ascopubs.org.
