In the phase III CheckMate 141 trial reported in The New England Journal of Medicine, Ferris et al found that nivolumab (Opdivo) increased overall survival vs standard therapies in patients with recurrent platinum-refractory squamous cell carcinoma of the head and neck.
In this open-label trial, 361 patients with disease progression within 6 months of platinum-based chemotherapy from sites in the United States, Europe, and elsewhere were randomized 2:1 between June 2014 and August 2015 to nivolumab at 3 mg/kg every 2 weeks (n = 240) or standard single-agent therapy (n = 121), including methotrexate (n = 46), docetaxel (n = 52), or cetuximab (Erbitux; n = 13). The primary endpoint was overall survival in the intent-to-treat population.
For the nivolumab and standard therapy groups, median age was 59 and 61 years; 82% and 85% were male; 82% and 86% were white and 12% in both groups were Asian; 80% and 70% were current or former smokers; the predominant tumor site was the oral cavity in 45% and 55%; at least 2 previous lines of systemic therapy had been received by 56% and 52%; and 63% and 60% had received prior cetuximab. Among 113 nivolumab patients and 65 standard therapy patients, 26% and 24% had positive human papillomavirus p16 status, respectively.
Improved Overall Survival
At interim analysis, the independent data-monitoring committee confirmed that the P value for the comparison of overall survival was below the statistical boundary for significance (.0227). Median follow-up for overall survival was 5.1 months (range = 0–16.8 months).
Median overall survival was 7.5 months (95% confidence interval [CI] = 5.5–9.1 months) in the nivolumab group vs 5.1 months (95% CI = 4.0–6.0 months) in the standard therapy group (hazard ratio [HR] = 0.70, P = .01). Overall survival at 1 year was 36.0% vs 16.6%. Median overall survival with nivolumab was at least numerically superior to that with methotrexate (4.6 months, HR = 0.64, 95% CI = 0.43–0.96), docetaxel (5.8 months, HR = 0.82, 95% CI = 0.53–1.28), and cetuximab (4.1 months, HR = 0.47, 95% CI = 0.22–1.01). Hazard ratios favored nivolumab in all prespecified demographic and clinical subgroups.
Among patients with PD-L1 (programmed cell death ligand 1) expression level ≥ 1%, median overall survival was 8.7 vs 4.6 months (HR = 0.55, 95% CI = 0.36–0.83); among those with an expression level < 1%, median overall survival was 5.7 vs 5.8 months (HR = 0.89, 95% CI = 0.54–1.45; P = .17 for interaction). Median overall survival was 9.1 vs 4.4 months (HR = 0.56, 95% CI = 0.32–0.99) among patients with p16-positive tumors and 7.5 vs 5.8 months (HR = 0.73, 95% CI = 0.42–1.25; P = .55 for interaction) among those with p16-negative tumors.
Median progression-free survival was 2.0 months vs 2.3 months (HR = 0.89, P = .32). Progression-free survival at 6 months was 19.7% vs 9.9%. The response rate was 13.3% vs 5.8%.
Treatment-related grade 3 or 4 adverse events occurred in 13.1% of nivolumab patients vs 35.1% of standard therapy patients. The most common treatment-related adverse events of any grade in the nivolumab group were fatigue (14.0%), nausea (8.5%), and rash (7.6%); the most common grade 3 or 4 events were fatigue (2.1%) and anemia (1.3%).
Among select adverse events, gastrointestinal events were less common with nivolumab (6.8% vs 14.4%), and skin adverse events (15.7% vs 12.6%) and adverse events of the endocrine system (7.6% vs 0.9%, primarily hypothyroidism) were more common with nivolumab. Pneumonitis occurred in 2.1% of nivolumab patients. Treatment-related deaths were reported in two nivolumab patients (due to pneumonitis and hypercalcemia) and one standard therapy patient (lung infection).
Physical, role, and social functioning on the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire–Core 30 module (QLQ-C30) were stable in the nivolumab group, whereas clinically meaningful worsening was observed in the standard therapy group.
The investigators concluded: “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.”
The study was funded by Bristol-Myers Squibb.
Robert L. Ferris, MD, PhD, of the University of Pittsburgh Cancer Institute, and Maura L. Gillison, MD, PhD, of The Ohio State University Comprehensive Cancer Center, contributed equally to The New England Journal of Medicine article.
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