@article{6439d4f3e2594ab3b208333206415842,
title = "Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC",
abstract = "Introduction: Durvalumab is a selective, high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 (PD-L1) binding to programmed death 1. Here we report safety and clinical activity in the NSCLC cohort of a phase I/II trial that included multiple tumor types (Study 1108; NCT01693562). Methods: Patients with stage IIIB–IV NSCLC (squamous or nonsquamous) received durvalumab 10 mg/kg every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. Primary objectives were safety and antitumor activity. Tumoral PD-L1 expression was assessed using the VENTANA SP263 Assay. Responses were assessed by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1). Adverse events were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (v4.03). Results: Of 304 patients, 79.0% were previously treated. Confirmed objective response rate was 21.8% in patients with greater than or equal to 25% PD-L1 expression and 6.4% in those with less than 25%; 25.9% in first-line patients and 12.7% in previously treated patients; and 14.0% in squamous and 16.7% in nonsquamous disease. Median overall survival was 12.4 months and median progression-free survival was 1.7 months; both were numerically longer in the PD-L1 greater than or equal to 25% group than in the PD-L1 less than 25% group (overall survival 16.4 versus 7.6 months, respectively; progression-free survival 2.6 versus 1.4 months, respectively). Treatment-related adverse events occurred in 57.2%, were grade 3/4 in 10.2%, and led to discontinuation in 5.6%. One patient (0.3%) died of treatment-related pneumonia with underlying pneumonitis. Conclusions: Durvalumab was clinically active irrespective of histology in this mostly pretreated population, with a manageable safety profile. Response rates and survival appeared to be enhanced in patients with greater tumoral PD-L1 expression.",
keywords = "Durvalumab, Efficacy, Immunotherapy, NSCLC, Safety",
author = "Antonia, {Scott J.} and Ani Balmanoukian and Julie Brahmer and Ou, {Sai Hong I.} and Hellmann, {Matthew D.} and Kim, {Sang We} and Ahn, {Myung Ju} and Kim, {Dong Wan} and Martin Gutierrez and Liu, {Stephen V.} and Patrick Sch{\"o}ffski and Dirk J{\"a}ger and Rahima Jamal and Guy Jerusalem and Jose Lutzky and John Nemunaitis and Luana Calabr{\`o} and Jared Weiss and Shirish Gadgeel and Jaishree Bhosle and Ascierto, {Paolo A.} and Rebelatto, {Marlon C.} and Rajesh Narwal and Meina Liang and Feng Xiao and Joyce Antal and Shaad Abdullah and Natasha Angra and Gupta, {Ashok K.} and Khleif, {Samir N.} and Segal, {Neil H.}",
note = "Funding Information: Disclosure: Dr. Antonia has participated on advisory boards with Bristol-Myers Squibb, Novartis, Merck, CBMG, Boehringer Ingelheim, FLX Bio, Nektar, AstraZeneca, Memgen, and Venn. Dr. Balmanoukian has received personal fees from AstraZeneca, Genentech, Merck, and Bristol-Myers Squibb. Dr. Brahmer has received grants from Bristol-Myers Squibb and AstraZeneca; and has received personal fees from AstraZeneca, Merck, Bristol-Myers Squibb, and Genentech. Dr. Ou is a member of the scientific advisory board and has stock ownership with TP Therapeutics; and has received personal fees from AstraZeneca, Pfizer, Roche, Foundation Medicine, Inc., and Takeda/ARIAD. Dr. Hellmann has received grants from Bristol-Myers Squibb; has received personal fees from AstraZeneca, Merck, Bristol-Myers Squibb, Genentech/Roche, Janssen, Nektar, Syndax, Mirati, and Shattuck Labs; and holds a licensed patent filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208). Dr. D.W. Kim has received personal fees from Novartis. Dr. Gutierrez has received personal fees from Bristol-Myers Squibb, Merck, Eli Lilly, Guardant 360, Esanex, Foundation Medicine, and AstraZeneca. Dr. Liu has received grants from AstraZeneca, Bayer, Blueprint, Clovis, Corvus, Esanex, Genentech/Roche, Lilly, Merck, Molecular Partners, OncoMed, Pfizer, and Threshold; and has received personal fees from AstraZeneca, Genentech/Roche, Lilly, Pfizer, Bristol-Myers Squibb, Celgene, Heron, Regeneron, Taiho, and Takeda/Ariad. Dr. Sch{\"o}ffski has received grants from Blueprint Medicines, Boehringer Ingelheim, Cobiores nv, Eisai, Eli Lilly, Exelixis, G1Therapeutics, Novartis, PharmaMar, and Plexxikon; and has received personal fees from 6th Element Capital, Adaptimmune, Amcure, Blueprint Medicines, Bristol-Myers Squibb, Deciphera, Eisai, Eli Lilly, Ellipses Pharma, Epizyme Pharma, Genzyme, Ipsen, Loxo Oncology, Medpace, Merck, Nektar, Piqur Therapeutics, Plexxikon, PharmaMar, and AstraZeneca. Dr. Jamal has received grants from AstraZeneca. Dr. Jerusalem has received grants from Novartis and Roche; and has received personal fees from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, Bristol-Myers Squibb, Puma Technology, AstraZeneca, Daiichi Sankyo, and AbbVie. Dr. Lutzky has received personal fees from Bristol-Myers Squibb. Dr. Nemunaitis has received personal fees from AstraZeneca. Dr. Weiss has received grants from AstraZeneca, Celgene, Merck, and Novartis; and has received personal fees from AstraZeneca, Celgene, Pfizer, Regeneron, and EMD Serono. Dr. Gadgeel has received personal fees from AstraZeneca, Genentech/Roche, AbbVie, Takeda, and Bristol-Myers Squibb. Dr. Bhosle has received nonfinancial support from AstraZeneca. Dr. Ascierto has served on advisory boards and/or provided consultancy for Bristol-Myers Squibb, Roche/Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, and Ultimovacs, and has received research funding from Bristol-Myers Squibb, Roche/Genentech, and Array. Drs. Rebelatto, Narwal, and Liang are employees of AstraZeneca, and own stock in AstraZeneca. Drs. Xiao, Antal, Abdullah, and Angra are employees of AstraZeneca. Dr. Gupta is an employee of AstraZeneca, owns stock in AstraZeneca and Bristol-Myers Squibb, and holds a patent for the use of immunotherapy in the treatment of cancer issued by Bristol-Myers Squibb. Dr. Khleif is a member of NewLink SAB and has a preclinical research agreement with Genentech. Dr. Segal has received grants from Roche/Genentech, Pfizer, Merck, Bristol-Myers Squibb, MedImmune/AstraZeneca, and Incyte; and has received personal fees from Roche/Genentech, Merck, Bristol-Myers Squibb, MedImmune/AstraZeneca, Boehringer Ingelheim, Pfizer, Pieris, PsiOxus, Synlogic, Aduro, Kyn Therapeutics, Pure Tech Ventures, Horizon Pharma, EMD Serono, Gritstone Oncology, Chugai, TRM Oncology, and IFM Therapeutics. The remaining authors declare no conflict of interest.This study was funded by AstraZeneca. Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, United Kingdom) and was funded by AstraZeneca (Gaithersburg, Maryland). The authors thank the patients, their families and caregivers, trial nurses, data managers, and all study investigators, including Drs. Joseph Leach and Wen Jen Hwu, for their contributions to study conduct. Funding Information: This study was funded by AstraZeneca . Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, United Kingdom) and was funded by AstraZeneca (Gaithersburg, Maryland). The authors thank the patients, their families and caregivers, trial nurses, data managers, and all study investigators, including Drs. Joseph Leach and Wen Jen Hwu, for their contributions to study conduct. Publisher Copyright: {\textcopyright} 2019 International Association for the Study of Lung Cancer",
year = "2019",
month = oct,
doi = "10.1016/j.jtho.2019.06.010",
language = "English (US)",
volume = "14",
pages = "1794--1806",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "10",
}