Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer

被引：332

作者：

Shitara, Kohei ^{[1
]}

Ajani, Jaffer A. ^{[2
]}

Moehler, Markus ^{[3
]}

Garrido, Marcelo ^{[4
]}

Gallardo, Carlos ^{[5
]}

Shen, Lin ^{[6
]}

Yamaguchi, Kensei ^{[7
]}

Wyrwicz, Lucjan ^{[8
]}

Skoczylas, Tomasz ^{[9
]}

Bragagnoli, Arinilda Campos ^{[10
]}

Liu, Tianshu ^{[11
]}

Tehfe, Mustapha ^{[12
]}

Elimova, Elena ^{[13
]}

Bruges, Ricardo ^{[14
]}

Zander, Thomas ^{[15
,16
]}

de Azevedo, Sergio ^{[17
]}

Kowalyszyn, Ruben ^{[18
]}

Pazo-Cid, Roberto ^{[19
]}

Schenker, Michael ^{[20
]}

Cleary, James M. ^{[21
]}

Yanez, Patricio ^{[22
]}

Feeney, Kynan ^{[23
]}

Karamouzis, Michalis, V ^{[24
]}

Poulart, Valerie ^{[25
]}

Lei, Ming ^{[25
]}

Xiao, Hong ^{[25
]}

Kondo, Kaoru ^{[25
]}

Li, Mingshun ^{[25
]}

Janjigian, Yelena Y. ^{[26
,27
]}

机构：

[1] Natl Canc Ctr Hosp East, Kashiwa, Chiba, Japan

[2] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[3] Johannes Gutenberg Univ Clin, Mainz, Germany

[4] Pontificia Univ Catolica, Unica San Carlos Apoquindo, Santiago, Chile

[5] Fdn Arturo Lopez Perez, Providencia, Chile

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

[7] Canc Inst Hosp JFCR, Tokyo, Japan

[8] Narodowy Inst Onkol, Klin Onkol & Radioterapii, Warsaw, Poland

[9] Med Univ Lublin, Klin Chirurgii Ogolnej Gastroenterol & Nowotworow, Lublin, Poland

[10] Fundacao Pio Xii Hosp Canc Barretos, Barretos, Brazil

[11] Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China

[12] Ctr Hosp Univ Montreal, Oncol Ctr, Montreal, PQ, Canada

[13] Princess Margaret Canc Ctr, Toronto, ON, Canada

[14] Inst Nacl Cancerol ESE, Bogota, Colombia

[15] Univ Cologne, Dept Internal Med, Ctr Integrated Oncol Aachen Bonn Cologne Duesseld, Cologne, Germany

[16] Gastrointestinal Canc Grp Cologne GCGC, Cologne, Germany

[17] Hos Clin Porto Alegre, Porto Alegre, RS, Brazil

[18] Clin Viedma SA, Inst Multidisciplinario Oncol, Viedma, Argentina

[19] Hosp Univ Rio Miguel Servet, Zaragoza, Spain

[20] SF Nectarie Oncol Ctr, Craiova, Romania

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

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

[23] St John God Murdoch Hosp, Murdoch, WA, Australia

[24] Laiko Gen Hosp Athens, Athens, Greece

[25] Bristol Myers Squibb, Princeton, NJ USA

[26] Mem Hosp Canc & Allied Dis, 1275 York Ave, New York, NY 10021 USA

[27] Weill Cornea Med Coll, New York, NY 10021 USA

来源：

NATURE | 2022年 / 603卷 / 7903期

关键词：

OPEN-LABEL; COMBINATION THERAPY; SOLID TUMORS; JUNCTION; CAPECITABINE; CISPLATIN;

D O I：

10.1038/s41586-022-04508-4

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：

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma(1-4). Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial(5) (programmed death ligand-1 (PD-L1) combined positive score >= 5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries(6). Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively(7-)(11). Treatment combining 1 mg kg(-1) nivolumab with 3 mg kg(-1) ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer(12). Here we report both long-term follow-up results comparing nivolumab plus chemotherapyversus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive >= 5 score (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score >= 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

引用

页码：942 / +

页数：21

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