Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH)

被引：380

作者：

Peters, Solange ^{[1
]}

Gettinger, Scott ^{[3
]}

Johnson, Melissa L. ^{[4
]}

Janne, Pasi A. ^{[5
]}

Garassino, Marina C. ^{[6
]}

Christoph, Daniel ^{[7
,8
]}

Toh, Chee Keong ^{[10
]}

Rizvi, Naiyer A. ^{[11
]}

Chaft, Jamie E. ^{[11
,12
]}

Carcereny Costa, Enric ^{[13
]}

Patel, Jyoti D. ^{[19
]}

Chow, Laura Q. M. ^{[20
]}

Koczywas, Marianna ^{[21
]}

Ho, Cheryl ^{[23
]}

Fruh, Martin ^{[2
]}

van den Heuvel, Michel ^{[27
]}

Rothenstein, Jeffrey ^{[24
]}

Reck, Martin ^{[9
]}

Paz-Ares, Luis ^{[14
,15
,16
]}

Shepherd, Frances A. ^{[25
,26
]}

Kurata, Takayasu ^{[28
]}

Li, Zhengrong ^{[22
]}

Qiu, Jiaheng ^{[22
]}

Kowanetz, Marcin ^{[22
]}

Mocci, Simonetta ^{[22
]}

Shankar, Geetha ^{[22
]}

Sandler, Alan ^{[22
]}

Felip, Enriqueta ^{[17
,18
]}

机构：

[1] CHU Vaudois, Lausanne, Switzerland

[2] Kantonsspital St Gallen, St Gallen, Switzerland

[3] Yale Canc Ctr, New Haven, CT USA

[4] Sarah Cannon Res Inst, Nashville, TN USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[7] Univ Duisburg Essen, Univ Klinikum Essen, Essen, Germany

[8] Univ Duisburg Essen, Ruhrlandklin, Essen, Germany

[9] German Ctr Lung Res DZL, Lung Clin Grosshansdorf, ARCN, Grosshansdorf, Germany

[10] Natl Canc Ctr, Singapore, Singapore

[11] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[12] Weill Cornell Med Coll, New York, NY USA

[13] Catalan Inst Oncol Badalona, Badalona, Spain

[14] Hosp Univ Doce Octubre, Madrid, Spain

[15] Ciberonc, CNIO, IIS I 12, Madrid, Spain

[16] Univ Complutense, Madrid, Spain

[17] Vall dHebron Univ Hosp, Barcelona, Spain

[18] Vall dHebron Inst Oncol, Barcelona, Spain

[19] Univ Chicago, Chicago, IL 60637 USA

[20] Univ Washington, Seattle, WA 98195 USA

[21] City Hope Natl Med Ctr, Duarte, CA USA

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

[23] BC Canc Agcy, Vancouver Ctr, Vancouver, BC, Canada

[24] RS McLaughlin Durham Reg Canc Ctr, Oshawa, ON, Canada

[25] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[26] Univ Toronto, Toronto, ON, Canada

[27] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands

[28] Kansai Med Univ, Hirakata Hosp, Osaka, Japan

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 24期

基金：

美国国家卫生研究院;

关键词：

LONG-TERM SAFETY; OPEN-LABEL; CLINICAL ACTIVITY; ANTIBODY; DOCETAXEL; CHEMOTHERAPY; NIVOLUMAB; PEMBROLIZUMAB; MULTICENTER; BEVACIZUMAB;

D O I：

10.1200/JCO.2016.71.9476

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on >= 5% of TC or IC (TC2/3 or IC2/3 [TC or IC >= 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab. (C) 2017 by American Society of Clinical Oncology

引用

页码：2781 / +

页数：16

共 30 条

[1]

[Anonymous], SAN ANT BREAST CANC

[2]

[Anonymous], 2015, J CLIN ONCOL S

[3]

Besse B, 2015, EUR CANC C VIENN AUS

[4]

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[5]

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[6]

Bristol-Myers Squibb, 2016, OPDIVO NIV PRESCR IN

[7]

Oncology Meets Immunology: The Cancer-Immunity Cycle [J].

Chen, Daniel S. ;

Mellman, Ira .

IMMUNITY, 2013, 39 (01) :1-10

[8]

Molecular Pathways: Next-Generation Immunotherapy-Inhibiting Programmed Death-Ligand 1 and Programmed Death-1 [J].

Chen, Daniel S. ;

Irving, Bryan A. ;

Hodi, F. Stephen .

CLINICAL CANCER RESEARCH, 2012, 18 (24) :6580-6587

[9]

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial [J].

Fehrenbacher, Louis ;

Spira, Alexander ;

Ballinger, Marcus ;

Kowanetz, Marcin ;

Vansteenkiste, Johan ;

Mazieres, Julien ;

Park, Keunchil ;

Smith, David ;

Artal-Cortes, Angel ;

Lewanski, Conrad ;

Braiteh, Fadi ;

Waterkamp, Daniel ;

He, Pei ;

Zou, Wei ;

Chen, Daniel S. ;

Yi, Jing ;

Sandler, Alan ;

Rittmeyer, Achim .

LANCET, 2016, 387 (10030) :1837-1846

[10]

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens [J].

Fossella, FV ;

DeVore, R ;

Kerr, RN ;

Crawford, J ;

Natale, RR ;

Dunphy, F ;

Kalman, L ;

Miller, V ;

Lee, JS ;

Moore, M ;

Gandara, D ;

Karp, D ;

Vokes, E ;

Kris, M ;

Kim, Y ;

Gamza, F ;

Hammershaimb, L .

JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (12) :2354-2362

← 1 2 3 →