Clinical Activity, Tolerability, and Long-Term Follow-Up of Durvalumab in Patients With Advanced NSCLC

被引：89

作者：

Antonia, Scott J. ^{[1
]}

Balmanoukian, Ani ^{[2
]}

Brahmer, Julie ^{[3
]}

Ou, Sai-Hong I. ^{[4
]}

Hellmann, Matthew D. ^{[5
]}

Kim, Sang-We ^{[6
]}

Ahn, Myung-Ju ^{[7
]}

Kim, Dong-Wan ^{[8
]}

Gutierrez, Martin ^{[9
]}

Liu, Stephen V. ^{[10
]}

Schoffski, Patrick ^{[11
]}

Jaeger, Dirk ^{[12
]}

Jamal, Rahima ^{[13
]}

Jerusalem, Guy ^{[14
]}

Lutzky, Jose ^{[15
,16
]}

Nemunaitis, John ^{[17
]}

Calabro, Luana ^{[18
]}

Weiss, Jared ^{[19
]}

Gadgeel, Shirish ^{[20
]}

Bhosle, Jaishree ^{[21
]}

Ascierto, Paolo A. ^{[22
]}

Rebelatto, Marlon C. ^{[23
]}

Narwal, Rajesh ^{[23
]}

Liang, Meina ^{[23
]}

Xiao, Feng ^{[23
]}

Antal, Joyce ^{[23
]}

Abdullah, Shaad ^{[23
]}

Angra, Natasha ^{[23
]}

Gupta, Ashok K. ^{[23
]}

Khleif, Samir N. ^{[24
]}

Segal, Neil H. ^{[5
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[2] Angeles Clin & Res Inst, Los Angeles, CA USA

[3] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[4] Univ Calif Irvine, Sch Med, Dept Med, Div Hematol Med Oncol, Irvine, CA 92717 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[6] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[7] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea

[8] Seoul Natl Univ Hosp, Seoul, South Korea

[9] Hackensack Univ, Med Ctr, Hackensack, NJ USA

[10] Georgetown Univ, Med Ctr, Washington, DC 20007 USA

[11] Univ Hosp Leuven, Leuven, Belgium

[12] Natl Ctr Tumorerkrankungen Heidelberg, Baden, Switzerland

[13] Univ Montreal, CHUM Res Ctr CRCHUM, CHUM, Hop Notre Dame, Montreal, PQ, Canada

[14] CHU Sart Tilman Liege, Liege, Belgium

[15] Univ Liege, Liege, Belgium

[16] Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA

[17] Univ Toledo, Coll Med & Life Sci, 2801 W Bancroft St, Toledo, OH 43606 USA

[18] Univ Hosp Siena, Ctr Immunooncol, Siena, Italy

[19] Univ North Carolina Hosp, Chapel Hill, NC USA

[20] Univ Michigan, Ann Arbor, MI 48109 USA

[21] Royal Marsden NHS Fdn Trust, London, England

[22] Ist Nazl Tumori IRCCS Fdn G Pascale, Naples, Italy

[23] AstraZeneca, Gaithersburg, MD USA

[24] Georgetown Univ, Med Sch, Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2019年 / 14卷 / 10期

关键词：

NSCLC; Safety; Efficacy; Immunotherapy; Durvalumab; CELL LUNG-CANCER; NIVOLUMAB; PEMBROLIZUMAB; DOCETAXEL; SAFETY; HEAD;

D O I：

10.1016/j.jtho.2019.06.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

引用

页码：1794 / 1806

页数：13

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