Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer

被引：207

作者：

Fehrenbacher, Louis ^{[1
]}

von Pawel, Joachim ^{[2
]}

Park, Keunchil ^{[3
]}

Rittmeyer, Achim ^{[4
]}

Gandara, David R. ^{[5
]}

Aix, Santiago Ponce ^{[6
]}

Han, Ji-Youn ^{[7
]}

Gadgeel, Shirish M. ^{[8
]}

Hida, Toyoaki ^{[9
]}

Cortinovis, Diego L. ^{[10
]}

Cobo, Manuel ^{[11
]}

Kowalski, Dariusz M. ^{[12
]}

De Marinis, Filippo ^{[13
]}

Gandhi, Mayank ^{[14
]}

Danner, Bradford ^{[14
]}

Matheny, Christina ^{[14
]}

Kowanetz, Marcin ^{[14
]}

He, Pei ^{[14
]}

Felizzi, Federico ^{[14
]}

Patel, Hina ^{[14
]}

Sandler, Alan ^{[14
]}

Ballinger, Marcus ^{[14
]}

Barlesi, Fabrice ^{[15
]}

机构：

[1] Kaiser Permanente Med Ctr, 975 Serena Dr, Vallejo, CA 94589 USA

[2] Asklepios Fachkliniken Munchen Gauting, Gauting, Germany

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

[4] Pulm Clin Immenhausen, Immenhausen, Germany

[5] Univ Calif Davis, Comprehens Canc Ctr, Sacramento, CA 95817 USA

[6] Univ Hosp 12 Octubre, Madrid, Spain

[7] Natl Canc Ctr, Goyang, South Korea

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

[9] Aichi Canc Ctr Hosp, Nagoya, Aichi, Japan

[10] Univ Hosp San Gerardo, Monza, Italy

[11] Carlos Haya Univ, Reg Malaga Hosp, Malaga, Spain

[12] Maria Sktodowska Curie Mem Canc Ctr Inst Oncol, Warsaw, Poland

[13] European Inst Oncol, Milan, Italy

[14] Genentech Inc, San Francisco, CA 94080 USA

[15] Aix Marseille Univ, AP HM, Marseille, France

来源：

JOURNAL OF THORACIC ONCOLOGY | 2018年 / 13卷 / 08期

关键词：

Atezolizumab; PD-L1; Checkpoint inhibitor; Non-small cell lung cancer; Cancer immunotherapy; OPEN-LABEL; MULTICENTER; NIVOLUMAB;

D O I：

10.1016/j.jtho.2018.04.039

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m(2), intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1-expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64-0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70-0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

引用

页码：1156 / 1170

页数：15

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