Author(s): Robert I. Haddad, MD1; Kevin Harrington, MBBS, PhD, FRCP2; Makoto Tahara, MD, PhD3; Robert L. Ferris, MD, PhD4; Maura Gillison, MD, PhD5; Jerome Fayette, MD, PhD6; Amaury Daste, MD7; Piotr Koralewski, MD8; Bogdan Zurawski, MD9; Miren Taberna, MD, PhD10; Nabil F. Saba, MD, FACP11; Milena Mak, MD, PhD12; Andrzej Kawecki, MD13; Gustavo Girotto, MD14; Miguel Angel Alvarez Avitia, MD15; Caroline Even, MD16; Joaquin Gabriel Reinoso Toledo, MD17; Alexander Guminski, MBBS, PhD, FRACP18; Urs Müller-Richter, MD, DMD, MDS19; Naomi Kiyota, MD, PhD20; Mustimbo Roberts, PhD21; Tariq Aziz Khan, MD21; Karen Miller-Moslin, PhD21; Li Wei, PhD21; and Athanassios Argiris, MD, FACP22,23
PURPOSE
CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
METHODS
Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations.
RESULTS
Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME.
CONCLUSION
CheckMate 651 did not meet its primary end points of OS 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 R/M SCCHN.
Author Affiliations
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA2Royal Marsden Hospital/The Institute of Cancer Research NIHR Biomedical Research Centre, London, United Kingdom3National Cancer Center Hospital East, Kashiwa, Japan4UPMC Hillman Cancer Center, Pittsburgh, PA5The University of Texas MD Anderson Cancer Center, Houston, TX6Centre Léon Bérard, Lyon, France7Hôpital Saint-André, Bordeaux, France8Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie, Krakow, Poland9Ambulatorium Chemioterapii, Bydgoszcz, Poland10Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain11Winship Cancer Institute of Emory University, Atlanta, GA12Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil13Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland14Hospital de Base de Sao Jose do Rio Preto, Sao Jose do Rio Preto, Brazil15Instituto Nacional De Cancerología, Mexico City, Mexico16Gustave Roussy, Villejuif, France17The Research Unit, Monterrey, Nuevo Leon, Mexico18Royal North Shore Hospital, Sydney, Australia19University Hospital Würzburg, Bavarian Cancer Research Center (BZKF), Würzburg, Germany20Kobe University Hospital, Kobe, Japan21Bristol Myers Squibb, Princeton, NJ22Hygeia Hospital, Marousi, Greece23Thomas Jefferson University, Philadelphia, PA
