• Dan P Zandberg, Alain P Algazi, Antonio Jimeno, James S Good, Jérôme Fayette, Nathaniel Bouganim, Neal E Ready, Paul M Clement, Caroline Even, Raymond W Jang, Stuart Wong, Ulrich Keilholz, Jill Gilbert, Moon Fenton, Irene Braña, Stephanie Henry, Eva Remenar, Zsuzsanna Papai, Lillian L Siu, Anthony Jarkowski, Jon M Armstrong, Kobby Asubonteng, Jean Fan, Giovanni Melillo, and Ricard Mesía.
• University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: zandbergdp@upmc.edu.
• Eur. J. Cancer. 2019 Jan 1; 107: 142-152.

BackgroundPatients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC.Patients And MethodsImmunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS).ResultsAmong evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9-24.4); 29.4% (95% CI, 15.1-47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5-21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9-3.7) and 7.1 months (95% CI, 4.9-9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5-22.1) and 33.6% (95% CI, 24.8-42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up.ConclusionDurvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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