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.)

Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).

No abstract

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting.

Background: Patients (pts) with platinum-refractory R/M SCCHN have an extremely poor prognosis and no chemotherapy (CT) options to extend survival. Nivo, a fully human anti-programmed death-1 monoclonal antibody, is FDA-approved and improves survival in other tumor types. Methods: A randomized, open-label, phase 3 trial (NCT02105636) assigned pts (stratified by prior cetuximab) with SCCHN who progressed within 6 mo of platinum-based CT in a 2:1 ratio to nivo 3 mg/kg Q2W or weekly single-agent IC (methotrexate 40-60 mg/m2, docetaxel 30-40 mg/m2, or cetuximab 400-mg/m2 loading dose followed by 250 mg/m2 weekly). Pts must not have received systemic therapy subsequent to biopsy and prior to screening. Pts could receive nivo beyond disease progression if there was evidence of clinical benefit. The primary endpoint was OS. Secondary endpoints were PFS and objective response rate (ORR) by RECIST 1.1. Additional endpoints included safety and outcomes by PD-L1 and HPV (p16 IHC) status. An interim analysis (IA) was planned after at least 195 deaths. Results: Of 361 randomized pts, median age was 60.0 yr, 76.5% were current/former smokers, 54.8% had received ?2 prior lines of CT, 91.4% had prior radiotherapy, and 98.3% had ECOG score ?1. At IA, 133 of 240 pts (55.4%) on nivo and 85 of 121 pts (70.2%) on IC had died. Nivo-treated pts had a 30% reduction in risk of death (HR, 0.70; 97.73% CI, 0.51-0.96; P = 0.010); median OS was 7.5 mo (95% CI, 5.5-9.1) with nivo vs 5.1 mo (95% CI, 4.0-6.0) with IC. Tumor PD-L1 status was evaluable in 260 pts (72.0%). Median OS in pts with PD-L1 ?1% was 8.7 mo with nivo vs 4.6 mo with IC (HR, 0.55; 95% CI, 0.36-0.83) and, in pts with PD-L1 <1%, 5.7 vs 5.8 mo, respectively (HR, 0.89; 95% CI, 0.54-1.45). HPV status by IHC was available in 178 pts (49.3%). Median OS in HPV+ pts was 9.1 mo with nivo vs. 4.4 mo with IC (HR, 0.56; 95% CI, 0.32-0.99) and 7.5 mo vs. 5.8 mo, respectively, in HPV- pts (HR, 0.73; 95% CI, 0.42-1.25). Treatment-related adverse events (TRAEs) of any grade occurred in 58.9% of pts on nivo vs 77.5% of pts on IC; TRAEs Grade 3-4 were reported in 13.1% vs 35.1% of pts, respectively. Two treatment-related deaths on the nivo arm and one on the IC arm occurred. Conclusions: Nivo improved OS in pts with platinum-refractory R/M SCCHN compared to single-agent IC therapy. Pts with PD-L1 ?1% and HPV+ pts had significantly longer median OS with nivo than with IC, but nivo was effective regardless of PD-L1 or HPV status. As the first immunotherapy agent to increase survival in a randomized phase 3 study in R/M SCCHN, nivo is a new standard of care option for these pts. Citation Format: Maura L. Gillison, George Blumenschein, Jérôme Fayette, Joel Guigay, A. Dimitrios Colevas, Lisa Licitra, Kevin Harrington, Stefan Kasper, Everett E. Vokes, Caroline Even, Francis Worden, Nabil F. Saba, Lara Carmen Iglesias Docampo, Robert Haddad, Tamara Rordorf, Naomi Kiyota, Makoto Tahara, Manish Monga, Mark Lynch, William J. Geese, Mark Schactman, Justin Kopit, James W. Shaw, Robert L. Ferris. Nivolumab (nivo) vs investigator's choice (IC) for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): CheckMate-141. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT099.