N Engl J Med 2016 11 8;375(19):1856-1867. Epub 2016 Oct 8.
From the University of Pittsburgh Medical Center and Cancer Institute, Pittsburgh (R.L.F.); the Department of Thoracic-Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.B.); Centre Leon Berard, Lyon (J.F.), Centre Antoine Lacassagne, Nice (J.G.), and Institut Gustave Roussy, Villejuif (C.E.) - all in France; Stanford Cancer Institute, Stanford, CA (A.D.C.); Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan (L.L.); Institute of Cancer Research-Royal Marsden National Institute for Health Research Biomedical Research Centre, London (K.H.); University Hospital Essen, Essen, Germany (S.K.); University of Chicago, Chicago (E.E.V.); University of Michigan, Ann Arbor (F.W.); Winship Cancer Institute of Emory University, Atlanta (N.F.S.); Hospital Universitario 12 de Octubre, Madrid (L.C.I.D.); Dana-Farber Cancer Institute, Boston (R.H.); Universitätsspital Zurich, Zurich, Switzerland (T.R.); Kobe University Hospital, Kobe (N.K.), and National Cancer Center Hospital East, Kashiwa (M.T.) - both in Japan; Bristol-Myers Squibb, Princeton, NJ (M.M., M.L., W.J.G., J.K., J.W.S.); and Ohio State University, Columbus (M.L.G.).
Background: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition.
Methods: In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life.
Results: The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P=0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P=0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group.
Conclusions: Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636 .).