Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Nov 10;375(19):1856-1867.
doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.

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

Robert L Ferris  1 , George Blumenschein Jr  1 , Jerome Fayette  1 , Joel Guigay  1 , A Dimitrios Colevas  1 , Lisa Licitra  1 , Kevin Harrington  1 , Stefan Kasper  1 , Everett E Vokes  1 , Caroline Even  1 , Francis Worden  1 , Nabil F Saba  1 , Lara C Iglesias Docampo  1 , Robert Haddad  1 , Tamara Rordorf  1 , Naomi Kiyota  1 , Makoto Tahara  1 , Manish Monga  1 , Mark Lynch  1 , William J Geese  1 , Justin Kopit  1 , James W Shaw  1 , Maura L Gillison  1
Affiliations
Clinical Trial

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

Robert L Ferris et al. N Engl J Med. .

Abstract

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 .).

PubMed Disclaimer

Figures

Figure 1
Figure 1. Overall Survival, Progression-free Survival, and Treatment Effect on Overall Survival According to Subgroup
Panel A shows the Kaplan–Meier curves for overall survival among all the patients who underwent randomization and were assigned to receive either nivolumab or standard therapy. In the planned interim analysis, the boundary for statistical significance for overall survival required the P value to be less than 0.0227. Panel B shows the Kaplan–Meier curves for progression-free survival among all the patients who underwent randomization. Symbols indicate censored observations. Hazard ratios (and confidence intervals) were computed with the use of a stratified Cox proportional-hazards model, and the P values were from a stratified log-rank test. Panel C shows a forest plot of unstratified hazard ratios for death in the analysis of the treatment effect according to demographic and clinical subgroups at baseline. Hazard ratios were not calculated for subgroups that included fewer than 20 patients across the two groups. Platinum-refractory disease in the context of primary therapy refers to cancer progression within 6 months after platinum therapy administered in the context of primary or adjuvant therapy (a post hoc derived analysis).
Figure 2
Figure 2. Overall Survival According to Baseline PD-L1 Status and Quality of Life and Symptom Burden
Kaplan–Meier curves for overall survival according to tumor programmed death 1 ligand 1 (PD-L1) expression of 1% or higher and of less than 1% are shown in Panels A and B, respectively. Symbols indicate censored observations. Hazard ratios (and 95% confidence intervals) were computed with the use of a Cox proportional-hazards model. Panel C shows the results of multivariable analyses of adjusted mean changes from baseline in patient-reported outcomes at weeks 9 and 15, stratified according to treatment group, for 129 patients with questionnaire responses. Least-squares mean estimates were based on analyses of covariance of changes in scores from baseline with adjustment for treatment group, visit, status with respect to previous cetuximab use, and baseline score. Physical, role, and social functioning were assessed by means of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 module (QLQ-C30), and pain, sensory problems, and social-contact problems were assessed by means of the EORTC head-and-neck–specific module (QLQ-H&N35). All scales range from 0 to 100 and were scored such that higher values indicated better functioning or lower symptom burden. A clinically meaningful score change was regarded as one of 10 points (dashed lines) or more., I bars indicate 95% confidence intervals.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. - PubMed
    1. Pignon JP, le Maître A, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92:4–14. - PubMed
    1. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350:1945–52. - PubMed
    1. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937–44. - PubMed
    1. Saloura V, Cohen EE, Licitra L, et al. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol. 2014;73:1227–39. - PubMed

Publication types

MeSH terms

Associated data