Recurrent Squamous-Cell Carcinoma of the Head and Neck

Original Article
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

Robert L. Ferris, M.D., Ph.D., George Blumenschein, Jr., M.D., Jerome Fayette, M.D., Ph.D., Joel Guigay, M.D., A. Dimitrios Colevas, M.D., Lisa Licitra, M.D., Kevin Harrington, Ph.D., F.R.C.P., F.R.C.R., Stefan Kasper, M.D., Everett E. Vokes, M.D., Caroline Even, M.D., Francis Worden, M.D., Nabil F. Saba, M.D., Lara C. Iglesias Docampo, M.D., Robert Haddad, M.D., Tamara Rordorf, M.D., Naomi Kiyota, M.D., Ph.D., Makoto Tahara, M.D., Ph.D., Manish Monga, M.D., Mark Lynch, Ph.D., William J. Geese, Ph.D., Justin Kopit, Ph.D., James W. Shaw, Pharm.D., Ph.D., M.P.H., and Maura L. Gillison, M.D., Ph.D.

October 9, 2016DOI: 10.1056/NEJMoa1602252

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.)