EAGLE: A phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Lisa F. Licitra Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy info_outline Lisa F. Licitra, Robert I. Haddad, Caroline Even, Makoto Tahara, Mikhail Dvorkin, Tudor-Eliade Ciuleanu, Paul M. Clement, Ricard Mesia, Svetlana I. Kutukova, Lyubov Zholudeva, Amaury Daste, Javier Daroqui Caballero, Bhumsuk Keam, Ihor Vynnychenko, Cedrik Lafond, Jagdish Shetty, Nassim Morsli, Helen Mann, Jerome Fayette, Robert L. Ferris

Authors Lisa F. Licitra Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy info_outline Lisa F. Licitra, Robert I. Haddad, Caroline Even, Makoto Tahara, Mikhail Dvorkin, Tudor-Eliade Ciuleanu, Paul M. Clement, Ricard Mesia, Svetlana I. Kutukova, Lyubov Zholudeva, Amaury Daste, Javier Daroqui Caballero, Bhumsuk Keam, Ihor Vynnychenko, Cedrik Lafond, Jagdish Shetty, Nassim Morsli, Helen Mann, Jerome Fayette, Robert L. Ferris Organizations Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, Gustave Roussy, Villejuif, France, National Cancer Center Hospital East, Kashiwa, Japan, Omsk Regional Clinical Centre of Oncology, Omsk, Russia, Institute of Oncology/University of Medicine and Pharmacy, Cluj-Napoca, Romania, Department of Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium, Catalan Institute of Oncology, IDIBELL, Barcelona, Spain, SPb SBIH City Clinical Oncology Dispensary, Saint-Petersburg, Russian Federation, Regional Transcarpathian Oncological Dispensary, Uzhgorod, Ukraine, Hôpital Saint André, University of Bordeaux-CHU, Bordeaux, France, Hospital Universitario La Fé, València, Spain, Department of Internal Medicine, Hemato-Oncology, Seoul National University Hospital, Seoul, South Korea, Sumy State University, Sumy Regional Oncology Center, Sumy, Ukraine, Clinique Victor Hugo, Le Mans, France, AstraZeneca, Gaithersburg, MD, AstraZeneca, Cambridge, United Kingdom, AstraZeneca, Macclesfield, United Kingdom, Centre Léon Bérard, Medical Oncology, Lyon, France, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874 D (n = 240) D+T (n = 247) SOC (n = 249) Median OS, mo (95% CI) 7.6 (6.1–9.8) 6.5 (5.5–8.2) 8.3 (7.3–9.2) Survival rate, % (95% CI) 12 mo 37.0 (30.9–43.1) 30.4 (24.7–36.3) 30.5 (24.7–36.4) 24 mo 18.4 (13.3–24.1) 13.3 (8.9–18.6) 10.3 (5.7–16.5) ORR, % (95% CI) 17.9 (13.3–23.3) 18.2 (13.6–23.6) 17.3 (12.8–22.6) DOR, mo 12.9 7.4 3.7