Original Research| Volume 109, P154-161, March 2019

Download started.


Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort

Published:February 04, 2019DOI:


      • Durvalumab monotherapy was safe in previously treated recurrent/metastatic head and neck squamous cell carcinoma.
      • Durable antitumour responses were observed, similar to other tumour cohorts.
      • Objective response rate and disease control rate were greater in patients with ≥25% vs <25% tumoural PD-L1 expression.



      Durvalumab selectively blocks programmed cell death ligand-1 (PD-L1) binding to programmed cell death-1. Encouraging clinical activity and manageable safety were reported in urothelial carcinoma, non–small-cell lung cancer (NSCLC), hepatocellular carcinoma (HC) and small-cell lung cancer (SCLC) in a multicenter phase I/II study. Safety and clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) were evaluated in the expansion phase.


      Patients received 10 mg/kg of durvalumab intravenously every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. The primary objective was safety; clinical activity was a secondary objective.


      Sixty-two patients were enrolled and evaluable (received first dose ≥24 weeks before data cutoff). Median age was 57 years; 40.3% were human papillomavirus (HPV)-positive; 32.3% had tumour cell PD-L1 expression ≥25%, and 62.9% were current/former smokers. They had a median of 2 prior systemic treatments (range, 1–13). All-causality adverse events (AEs) occurred in 98.4%; drug-related AEs occurred in 59.7% and were grade III–IV in 9.7%. There were no drug-related discontinuations or deaths. Objective response rate (blinded independent central review) was 6.5% (15.0% for PD-L1 ≥25%, 2.6% for <25%). Median time to response was 2.7 months (range, 1.2–5.5); median duration was 12.4 months (range, 3.5–20.5+). Median progression-free survival was 1.4 months; median overall survival (OS) was 8.4 months. OS rate was 62% at 6 months and 38% at 12 months (42% for PD-L1 ≥25%, 36% for <25%).


      Durvalumab safety in HNSCC was manageable and consistent with other cohorts of the study. Early, durable responses in these heavily pretreated patients warrant further investigation; phase III monotherapy and combination therapy studies are ongoing.

      Clinical trial registry NCT01693562; MedImmune study 1108.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Forster M.D.
        • Devlin M.J.
        Immune checkpoint inhibition in head and neck cancer.
        Front Oncol. 2018; 8: 310
        • Ishii H.
        • Tanaka S.
        • Masuyama K.
        Therapeutic strategy for cancer immunotherapy in head and neck cancer.
        Adv Cellular Mol Otolaryngol. 2015; 3: 1
        • Szturz P.
        • Vermorken J.B.
        Immunotherapy in head and neck cancer: aiming at EXTREME precision.
        BMC Med. 2017; 15: 110
        • Stransky N.
        • Egloff A.M.
        • Tward A.D.
        • Kostic A.D.
        • Cibulskis K.
        • Sivachenko A.
        • et al.
        The mutational landscape of head and neck squamous cell carcinoma.
        Science. 2011; 333: 1157-1160
        • Pai S.I.
        • Westra W.H.
        Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment.
        Annu Rev Pathol. 2009; 4: 49-70
        • Michmerhuizen N.L.
        • Birkeland A.C.
        • Bradford C.R.
        • Brenner J.C.
        Genetic determinants in head and neck squamous cell carcinoma and their influence on global personalized medicine.
        Genes Cancer. 2016; 7: 182-200
        • Albers A.E.
        • Strauss L.
        • Liao T.
        • Hoffmann T.K.
        • Kaufmann A.M.
        T cell‒tumor interaction directs the development of immunotherapies in head and neck cancer.
        Clin Dev Immunol. 2010; 2010: 236378
        • Chen D.S.
        • Irving B.A.
        • Hodi F.S.
        Molecular pathways: next-generation immunotherapy ‒ inhibiting programmed death-ligand 1 and programmed death-1.
        Clin Canc Res. 2012; 18: 6580-6587
        • Stewart R.
        • Morrow M.
        • Hammond S.A.
        • Mulgrew K.
        • Marcus D.
        • Poon E.
        • et al.
        Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody.
        Cancer Immunol Res. 2015; 3: 1052-1062
        • Feldman R.
        • Gatalica Z.
        • Knezetic J.
        • Reddy S.
        • Nathan C.A.
        • Javadi N.
        • et al.
        Molecular profiling of head and neck squamous cell carcinoma.
        Head Neck. 2016; 38: E1625-E1638
        • Ferris R.L.
        Immunology and immunotherapy of head and neck cancer.
        J Clin Oncol. 2015; 33: 3293-3304
        • Ibrahim R.
        • Stewart R.
        • Shalabi A.
        PD-L1 blockade for cancer treatment: MEDI4736.
        Semin Oncol. 2015; 42: 474-483
        • Powles T.
        • O'Donnell P.H.
        • Massard C.
        • Arkenau H.-T.
        • Friedlander T.W.
        • Hoimes C.
        • et al.
        Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma.
        J Clin Oncol. 2017; 35: 286
        • Antonia S.J.
        • Brahmer J.R.
        • Balmanoukian A.S.
        • Kim D.-W.
        • Kim S.-W.
        • Ahn M.-J.
        • et al.
        Safety and clinical activity of first-line durvalumab in advanced NSCLC: updated results from a Phase 1/2 study.
        J Clin Oncol. 2017; 35: e20504
        • Balmanoukian A.S.
        • Antonia S.J.
        • Hwu W.-J.
        • Hamid O.
        • Gutierrez M.
        • Jamal R.
        • et al.
        Updated safety and clinical activity of durvalumab monotherapy in previously treated patients with stage IIIB/IV NSCLC.
        J Clin Oncol. 2017; 35: 9085
        • Wainberg Z.A.
        • Segal N.H.
        • Jaeger D.
        • Lee K.-H.
        • Marshall J.
        • Antonia S.J.
        • et al.
        Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC).
        J Clin Oncol. 2017; 35: 4071
        • Goldman J.W.
        • Dowlati A.
        • Antonia S.
        • Nemunaitis J.
        • Butler M.
        • Segal N.
        • et al.
        Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC).
        in: Poster presentation at the annual meeting of the American society of clinical oncology. ASCO, Chicago, IL, USA, June 1‒52018 (abstr 8518)
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • Schwartz L.H.
        • Sargent D.
        • Ford R.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247
        • Rebelatto M.C.
        • Midha A.
        • Mistry A.
        • Sabalos C.
        • Schechter N.
        • Li X.
        • et al.
        Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma.
        Diagn Pathol. 2016; 11: 95
      1. National cancer Institute (NCI): common terminology criteria for adverse events (CTCAE) version 4.03. NCI, Rockville, MD2010
        • Brahmer J.R.
        • Tykodi S.S.
        • Chow L.Q.
        • Hwu W.J.
        • Topalian S.L.
        • Hwu P.
        • et al.
        Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
        N Engl J Med. 2012; 366: 2455-2465
        • Herbst R.S.
        • Soria J.C.
        • Kowanetz M.
        • Fine G.D.
        • Hamid O.
        • Gordon M.S.
        • et al.
        Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.
        Nature. 2014; 515: 563-567
        • Gettinger S.
        • Rizvi N.A.
        • Chow L.Q.
        • Borghaei H.
        • Brahmer J.
        • Ready N.
        • et al.
        Nivolumab monotherapy for first-line treatment of advanced non-small-cell lung cancer.
        J Clin Oncol. 2016; 34: 2980-2987
        • Borghaei H.
        • Paz-Ares L.
        • Horn L.
        • Spigel D.R.
        • Steins M.
        • Ready N.E.
        • et al.
        Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
        N Engl J Med. 2015; 373: 1627-1639
        • Hui R.
        • Garon E.B.
        • Goldman J.W.
        • Leighl N.B.
        • Hellmann M.D.
        • Patnaik A.
        • et al.
        Pembrolizumab as first-line therapy for patients with PD-L1-positive advanced non-small cell lung cancer: a phase 1 trial.
        Ann Oncol. 2017; 28: 874-881
        • Gulley J.L.
        • Rajan A.
        • Spigel D.R.
        • Iannotti N.
        • Chandler J.
        • Wong D.J.L.
        • et al.
        Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.
        Lancet Oncol. 2017; 18: 599-610
        • Chow L.Q.M.
        • Haddad R.
        • Gupta S.
        • Mahipal A.
        • Mehra R.
        • Tahara M.
        • et al.
        Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the Phase Ib KEYNOTE-012 expansion cohort.
        J Clin Oncol. 2016; 34: 3838-3845
        • Ferris R.L.
        • Blumenschein Jr., G.
        • Fayette J.
        • Guigay J.
        • Colevas A.D.
        • Licitra L.
        • et al.
        Nivolumab for recurrent squamous-cell carcinoma of the head and neck.
        N Engl J Med. 2016; 375: 1856-1867
        • Siu L.
        • Even C.
        • Mesía R.
        • Remenar E.
        • Daste A.
        • Delord J.-P.
        • et al.
        Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1–low/negative recurrent or metastatic HNSCC: the Phase 2 CONDOR randomized trial.
        JAMA Oncol. 2018; Nov 1; ([epub ahead of print])
        • Zandberg D.P.
        • Algazi A.
        • Jimeno A.
        • Good J.S.
        • Fayette J.
        • Bouganim N.
        • et al.
        Durvalumab for recurrent/metastatic HNSCC: results from a single-arm, phase 2 study (HAWK).
        in: Abstract presented at the Annual Meeting of the European Society for Medical Oncology (ESMO), Madrid, Spain, September 8‒12. 2017 (abstr 10420)