Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study.

Abstract Background Targeting the programmed cell death protein 1 (PD-1)/ligand (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated efficacy of durvalumab (an anti-PD-L1 mAb) or durvalumab plus tremelimumab (an anti-CTLA-4 mAb) versus standard of care (SoC) in R/M HNSCC patients. Patients and methods Patients were randomized 1:1:1 to durvalumab [10 mg/kg every 2 weeks (Q2W)], durvalumab plus tremelimumab (durvalumab 20 mg/kg Q4W plus tremelimumab 1 mg/kg Q4W × 4, then durvalumab 10 mg/kg Q2W), or SoC (cetuximab, a taxane, methotrexate or a fluoropyrimidine). The primary endpoints were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary endpoints included progression-free survival (PFS), objective response rate, and duration of response. Results Patients were randomized to durvalumab (n=240), durvalumab plus tremelimumab (n=247), or SoC (n=249). No statistically significant improvements in OS were observed for durvalumab versus SoC (HR: 0.88; 95% CI: 0.72–1.08; P=0.20) or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85–1.26; P=0.76). The 12-month survival rates (95% CI) were 37.0% (30.9–43.1), 30.4% (24.7–36.3) and 30.5% (24.7–36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related AEs (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively) and anemia (17.5%) for SoC. Grade ≥3 trAE rates were 10.1%, 16.3% and 24.2% for durvalumab, durvalumab plus tremelimumab and SoC, respectively. Conclusion There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab.