Nivolumab, an anti-PD-1 monoclonal antibody, was evaluated in a phase 3 trial for recurrent squamous-cell carcinoma of the head and neck in patients who had progressed after platinum-based chemotherapy. The trial randomly assigned 361 patients to receive nivolumab (3 mg/kg every 2 weeks) or standard therapy (methotrexate, docetaxel, or cetuximab). The primary endpoint was overall survival, with secondary endpoints including progression-free survival, objective response rate, safety, and quality of life. Nivolumab significantly improved overall survival compared to standard therapy, with a median survival of 7.5 months versus 5.1 months. The 1-year survival rate was 36.0% with nivolumab versus 16.6% with standard therapy. Progression-free survival was also improved, with 19.7% at 6 months versus 9.9% with standard therapy. The response rate was 13.3% with nivolumab versus 5.8% with standard therapy. Nivolumab was associated with fewer grade 3 or 4 adverse events (13.1% vs. 35.1%) and better quality of life measures. The trial showed that nivolumab improved survival and quality of life in patients with platinum-refractory squamous-cell carcinoma of the head and neck. Biomarker analysis indicated that nivolumab was effective regardless of PD-L1 expression or p16 status. The results suggest that nivolumab is a promising treatment option for this difficult-to-treat population. The study was funded by Bristol-Myers Squibb and registered as CheckMate 141.Nivolumab, an anti-PD-1 monoclonal antibody, was evaluated in a phase 3 trial for recurrent squamous-cell carcinoma of the head and neck in patients who had progressed after platinum-based chemotherapy. The trial randomly assigned 361 patients to receive nivolumab (3 mg/kg every 2 weeks) or standard therapy (methotrexate, docetaxel, or cetuximab). The primary endpoint was overall survival, with secondary endpoints including progression-free survival, objective response rate, safety, and quality of life. Nivolumab significantly improved overall survival compared to standard therapy, with a median survival of 7.5 months versus 5.1 months. The 1-year survival rate was 36.0% with nivolumab versus 16.6% with standard therapy. Progression-free survival was also improved, with 19.7% at 6 months versus 9.9% with standard therapy. The response rate was 13.3% with nivolumab versus 5.8% with standard therapy. Nivolumab was associated with fewer grade 3 or 4 adverse events (13.1% vs. 35.1%) and better quality of life measures. The trial showed that nivolumab improved survival and quality of life in patients with platinum-refractory squamous-cell carcinoma of the head and neck. Biomarker analysis indicated that nivolumab was effective regardless of PD-L1 expression or p16 status. The results suggest that nivolumab is a promising treatment option for this difficult-to-treat population. The study was funded by Bristol-Myers Squibb and registered as CheckMate 141.