@article{192d3fbf832c4630980a3530e85d8426,
title = "Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort",
abstract = "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.",
keywords = "Checkpoint inhibition, Head and neck squamous cell carcinoma, Human papillomavirus, Immunotherapy, PD-L1",
author = "Segal, {Neil H.} and Ou, {Sai Hong I.} and Ani Balmanoukian and Fury, {Matthew G.} and Erminia Massarelli and Brahmer, {Julie R.} and Jared Weiss and Patrick Sch{\"o}ffski and Antonia, {Scott J.} and Christophe Massard and Zandberg, {Dan P.} and Khleif, {Samir N.} and Feng Xiao and Rebelatto, {Marlon C.} and Steele, {Keith E.} and Robbins, {Paul B.} and Natasha Angra and Xuyang Song and Shaad Abdullah and Marcus Butler",
note = "Funding Information: N.H.S. served on the advisory boards of Roche/Genentech, Merck, Bristol-Myers Squibb, MedImmune/AstraZeneca, Boehringer-Ingelheim, Pfizer, Pieris, PsiOxus, Synlogic, Aduro, Kyn Therapeutics, PureTechVentures, Horizon Pharma, EMD Serono, Gritstone Oncology, Chugai, TRM oncology and IFM therapeutics; and received research funding from Roche / Genentech , Pfizer , Merck , Bristol-Myers Squibb , MedImmune / AstraZeneca and Incyte . S.-H.I.O. received honoraria from Roche/Genentech, AstraZeneca, Pfizer and Takeda/Ariad; had a consulting or advisory role at Roche/Genentech, AstraZeneca, Pfizer and Takeda/Ariad; served on the speakers' bureaus of Roche/Genentech, AstraZeneca, Pfizer and Takeda/Ariad and received research funding from Roche / Genentech , AstraZeneca , Pfizer , Takeda / Ariad , Blueprint Medicines and TP Therapeutics . A.B. served on the speakers' bureaus of Bristol-Myers Squibb, Merck, AstraZeneca and Genentech. M.G.F. is an employee of Regeneron Pharmaceuticals; has stock ownership in Regeneron Pharmaceuticals; received patents, royalties and other intellectual property from Regeneron Pharmaceuticals and received travel, accommodations and expenses from Regeneron Pharmaceuticals. E.M. received honoraria from Genentech, AstraZeneca and Merck; had a consulting or advisory role at Genentech; served on the speakers' bureaus of AstraZeneca and Merck; received research funding from Genentech , AstraZeneca , Bristol-Myers Squibb , Pfizer , Tessa , GlaxoSmithKline and Merck and received reimbursement for travel, accommodations and expenses from Genentech, AstraZeneca and Merck. J.R.B. had a consulting or advisory role at Bristol-Myers Squibb (uncompensated), Amgen, Celgene, Eli Lilly and Merck; and received research funding from MedImmune / AstraZeneca , Bristol-Myers Squibb and Merck . J.W. had a consulting or advisory role at Pfizer, EMD Serono, AstraZeneca, Celgene, Genetech and Boston Biomedical and received research funding from AstraZeneca , Celgene and Merck . P.S. had a consulting or advisory role at 6th Element Capital, Adaptimmune, Amcure, Blueprint Medicines, Bristol-Myers Squibb, Deciphera, Eisai, Eli Lilly, Ellipses Pharma, Epizyme, Genzyme, Ipsen, Loxo Oncology, Medpace, Merck, Nektar, Piqur Therapeutics and Plexxikon; served on the speaker's bureau of Eisai, PharmaMar and Eli Lilly; received research funding from Blueprint Medicines , Boehringer-Ingelheim , Cobiores NV , Eisai , Eli Lilly , Exelixis , G1 Therapeutics , Novartis , PharmaMar and Plexxikon and received reimbursement for travel, accommodations and expenses from 6th Element Capital, Adaptimmune, Amcure, AstraZeneca, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Epizyme, Genzyme, GlaxoSmithKline, Ipsen, Loxo Oncology, Medpace, Nektar, Novartis, PharmaMar, Philogen, Piqur Therapeutics and Plexxikon. S.J.A. owns stock in Cellular Biomedicine Group; received patents, royalties and other intellectual property from Cellular Biomedicine Group; had a consulting or advisory role at Bristol-Myers Squibb, Novartis, Merck, Cellular Biomedicine Group, Boehringer-Ingelheim, MedImmune/AstraZeneca, Memgen and FLX Bio and received research funding from AstraZeneca and Novartis . C.M. had a consulting or advisory role at Amgen, Astellas, AstraZeneca, Bayer, Celgene, Genentech, Ipsen, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi and Orion. D.P.Z. received research funding from Merck , AstraZeneca , Bristol-Myers Squibb , MedImmune and Neurogenics . S.N.K. is an employee of Abraaj; has a leadership role at Advaxis; has stock or other ownership at Advaxis, Northwest Bio and IO Biotech; received honoraria from Advaxis, IO Biotech, Syndax and Bioline Therapeutics; has a consulting or advisory role at IO Biotech, Syndax, Bioline Therapeutics, PDS Biotechnology and KAHR Medical; received research funding from AstraZeneca , Syndax , IO Biotech , Bioline , and Lycera and received patents, royalties and other intellectual property from Georgiamune. F.X. is an employee of MedImmune and owns stock in AstraZeneca. M.C.R. is an employee of MedImmune. K.E.S. is an employee of MedImmune; owns stock in AstraZeneca and received patents, royalties and other intellectual property from MedImmune. P.B.R. is a former employee of MedImmune and current employee of Pfizer Inc; owns stock in Pfizer, AstraZeneca, Merck and Bristol-Myers Squibb and received patents, royalties and other intellectual property from MedImmune / AstraZeneca . N.A. is an employee of MedImmune; owns stock in AstraZeneca; received reimbursement for travel, accommodations and expenses from MedImmune/AstraZeneca and received research funding from MedImmune / AstraZeneca . X.S. is an employee of MedImmune; owns stock in AstraZeneca and received reimbursement for travel, accommodations and expenses from MedImmune/AstraZeneca. S.A. is an employee of MedImmune and received reimbursement for travel, accommodations and expenses from MedImmune. M.B. received honoraria from Novartis, Merck and Bristol-Myers Squibb; had a consulting or advisory role at Merck Canada, Bristol-Myers Squibb Canada, EMD Serono, Immunocore, Novartis and Immunovaccine and received research funding from Merck and Takara . Funding Information: The authors thank the patients, their families and caregivers and all investigators involved in this study. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Susanne Gilbert, MA, of Cirrus Communications (New York, NY, USA) and was funded by MedImmune . The authors thank Ms. Anmarie Boutrin for expert management of patient tumour biopsy specimens. ",
year = "2019",
month = mar,
doi = "10.1016/j.ejca.2018.12.029",
language = "English (US)",
volume = "109",
pages = "154--161",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}