The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

被引：579

作者：

Janjigian, Yelena Y. ^{[1
,2
]}

Kawazoe, Akihito ^{[3
]}

Yanez, Patricio ^{[4
]}

Li, Ning ^{[5
]}

Lonardi, Sara ^{[6
]}

Kolesnik, Oleksii ^{[7
]}

Barajas, Olga ^{[8
]}

Bai, Yuxian ^{[9
]}

Shen, Lin ^{[10
]}

Tang, Yong ^{[11
]}

Wyrwicz, Lucjan S. ^{[12
]}

Xu, Jianming ^{[13
]}

Shitara, Kohei ^{[3
]}

Qin, Shukui ^{[14
]}

Van Cutsem, Eric ^{[15
,16
]}

Tabernero, Josep ^{[17
,18
]}

Li, Lie ^{[19
]}

Shah, Sukrut ^{[19
]}

Bhagia, Pooja ^{[19
]}

Chung, Hyun Cheol ^{[20
]}

机构：

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

[2] Weill Cornea Med Coll, New York, NY 10065 USA

[3] Natl Canc Hosp East, Kashiwa, Chiba, Japan

[4] Univ La Frontera, James Lind Canc Res Ctr, Temuco, Chile

[5] Zhengzhou Univ, Affiliated Canc Hosp, Henan Canc Hosp, Zhengzhou, Peoples R China

[6] Ist OncoL Veneto IOV IRCCS, Padua, Italy

[7] Med Ctr Oncolife, Zaporizhzhia, Ukraine

[8] Arturo Lopez Perez Fdn, Santiago, Chile

[9] Harbin Med Univ, Canc Hosp, Harbin, Peoples R China

[10] Peking Univ, Minist Educ Beijing, Key Lab Carcinogenesis & TransLat Res, Dept Gastrointestinal Oncol,Canc Hosp & Inst, Beijing, Peoples R China

[11] Xinjiang Med Univ, Canc Hosp, Urumqi, Xinjiang, Peoples R China

[12] Maria Sklodowska Curie Natl Canc Res Inst, Warsaw, Poland

[13] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Beijing, Peoples R China

[14] Canc Ctr Peoples Liberat Army, Nanjing, Peoples R China

[15] Univ Hosp Gasthuisberg, Leuven, Belgium

[16] Katholieke Univ Leuven, Leuven, Belgium

[17] Vall dHebron Hosp Campus, Barcelona, Spain

[18] UVic UCC, Inst Oncol VH10, IOB Quiron, Barcelona, Spain

[19] Merck & Co Inc, Kenilworth, NJ USA

[20] Yonsei Univ, Yonsei Canc Ctr, Coll Med, Seoul, South Korea

来源：

NATURE | 2021年 / 600卷 / 7890期

基金：

美国国家卫生研究院;

关键词：

NIVOLUMAB PLUS CHEMOTHERAPY; GASTROESOPHAGEAL JUNCTION; RESPONSE CRITERIA; OPEN-LABEL; TRASTUZUMAB; ESOPHAGEAL; THERAPY;

D O I：

10.1038/s41586-021-04161-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas(1-3). More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours(4). Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer(5), there are preclinical(6-19) and clinical(20,21) rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plustrastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma 22 (https://clinicaltrials.gov, NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.

引用

页码：727 / +

页数：16

共 32 条

[31] Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to Preoperative Trastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer [J].

Varadan, Vinay ;

Gilmore, Hannah ;

Miskimen, Kristy L. S. ;

Tuck, David ;

Parsai, Shikha ;

Awadallah, Amad ;

Krop, Ian E. ;

Winer, Eric P. ;

Bossuyt, Veerle ;

Somlo, George ;

Abu-Khalaf, Maysa M. ;

Fenton, Mary Anne ;

Sikov, William ;

Harris, Lyndsay N. .

CLINICAL CANCER RESEARCH, 2016, 22 (13) :3249-3259

[32]

zum Büschenfelde CM, 2002, CANCER RES, V62, P2244

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