PMID- 30731276 OWN - NLM STAT- MEDLINE DCOM- 20200521 LR - 20200521 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 109 DP - 2019 Mar TI - Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. PG - 154-161 LID - S0959-8049(19)30007-3 [pii] LID - 10.1016/j.ejca.2018.12.029 [doi] AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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: clinicaltrials.gov NCT01693562; MedImmune study 1108. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Segal, Neil H AU - Segal NH AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: segaln@mskcc.org. FAU - Ou, Sai-Hong I AU - Ou SI AD - Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology/Oncology, University of California School of Medicine, Orange, CA, USA. FAU - Balmanoukian, Ani AU - Balmanoukian A AD - Hematology/Oncology, The Angeles Clinic and Research Institute, Los Angeles, CA, USA. FAU - Fury, Matthew G AU - Fury MG AD - Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Massarelli, Erminia AU - Massarelli E AD - Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Brahmer, Julie R AU - Brahmer JR AD - Thoracic Oncology Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. FAU - Weiss, Jared AU - Weiss J AD - Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. FAU - Schoffski, Patrick AU - Schoffski P AD - Department of Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. FAU - Antonia, Scott J AU - Antonia SJ AD - Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA. FAU - Massard, Christophe AU - Massard C AD - Universite Paris Saclay, Universite Paris-Sud, Drug Development Department, Gustave Roussy, Villejuif, France. FAU - Zandberg, Dan P AU - Zandberg DP AD - Head and Neck and Thyroid Cancer Disease Sections, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA. FAU - Khleif, Samir N AU - Khleif SN AD - Georgia Cancer Center, Augusta University, Augusta, GA, USA. FAU - Xiao, Feng AU - Xiao F AD - Biostatistics, MedImmune, Gaithersburg, MD, USA. FAU - Rebelatto, Marlon C AU - Rebelatto MC AD - Translational Sciences, MedImmune, Gaithersburg, MD, USA. FAU - Steele, Keith E AU - Steele KE AD - Translational Sciences, MedImmune, Gaithersburg, MD, USA. FAU - Robbins, Paul B AU - Robbins PB AD - Translational Sciences, MedImmune, Gaithersburg, MD, USA. FAU - Angra, Natasha AU - Angra N AD - Clinical Development, MedImmune, Gaithersburg, MD, USA. FAU - Song, Xuyang AU - Song X AD - Translational Sciences, MedImmune, Gaithersburg, MD, USA. FAU - Abdullah, Shaad AU - Abdullah S AD - Clinical Development, MedImmune, Gaithersburg, MD, USA. FAU - Butler, Marcus AU - Butler M AD - Tumor Immunotherapy Program, Princess Margaret Cancer Centre, Toronto, ON, Canada. LA - eng SI - ClinicalTrials.gov/NCT01693562 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20190204 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents, Immunological) RN - 28X28X9OKV (durvalumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*therapeutic use MH - Antineoplastic Agents, Immunological/*therapeutic use MH - Female MH - Follow-Up Studies MH - Head and Neck Neoplasms/*drug therapy/pathology MH - Humans MH - Male MH - Middle Aged MH - Patient Safety MH - Prognosis MH - Retrospective Studies MH - Squamous Cell Carcinoma of Head and Neck/*drug therapy/pathology MH - Survival Rate MH - Young Adult OTO - NOTNLM OT - Checkpoint inhibition OT - Head and neck squamous cell carcinoma OT - Human papillomavirus OT - Immunotherapy OT - PD-L1 EDAT- 2019/02/08 06:00 MHDA- 2020/05/22 06:00 CRDT- 2019/02/08 06:00 PHST- 2018/09/11 00:00 [received] PHST- 2018/11/30 00:00 [revised] PHST- 2018/12/26 00:00 [accepted] PHST- 2019/02/08 06:00 [pubmed] PHST- 2020/05/22 06:00 [medline] PHST- 2019/02/08 06:00 [entrez] AID - S0959-8049(19)30007-3 [pii] AID - 10.1016/j.ejca.2018.12.029 [doi] PST - ppublish SO - Eur J Cancer. 2019 Mar;109:154-161. doi: 10.1016/j.ejca.2018.12.029. Epub 2019 Feb 4.