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科学家完成nivolumab加化疗或ipilimumab治疗胃-食道癌的临床试验
2022-03-27 19:28
来源：小柯机器人

美国纪念斯隆-凯特琳癌症中心Yelena Y. Janjigian团队完成nivolumab加化疗或ipilimumab治疗胃-食道癌的临床试验。2022年3月23日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，标准的一线化疗导致大多数人类表皮生长因子受体2（HER2）阴性的胃-食道腺癌患者在一年内出现疾病进展和死亡。nivolumab加化疗在随机、全球CheckMate 649 3期试验（程序性死亡配体-1（PD-L1）联合阳性评分≥5和所有随机患者）中，显示了胃、胃食管交界处或食管腺癌12个月随访时的总生存期优于化疗。基于这些结果，nivolumab加化疗现在在许多国家被批准作为这些患者的一线治疗方法。Nivolumab和细胞毒性T淋巴细胞抗原-4（CTLA-4）抑制剂ipilimumab具有不同但互补的作用机制，分别有助于恢复抗肿瘤T细胞功能和诱导新的抗肿瘤T细胞反应。结合1mg kg-1 nivolumab和3mg kg-1 ipilimumab的治疗在晚期胃食管癌患者中表现出有临床意义的抗肿瘤活性和可控的安全性。
 
研究人员报告了nivolumab加化疗与单独化疗的长期随访结果，以及CheckMate 649中nivolumab加ipilimumab与单独化疗的首次比较结果。在24.0个月的最低随访后，在PD-L1联合阳性评分≥5的患者（危险比0.70；95%置信区间0.61，0.81）和所有随机患者（危险比0.79；95%置信区间0.71，0.88）中，nivolumab加化疗与单用化疗相比，继续显示出总生存的改善。在PD-L1联合阳性评分≥5的患者中，nivolumab加ipilimumab与单独化疗相比，总生存率没有达到预设的意义界限。没有发现新的安全信号。这些结果支持继续使用nivolumab加化疗作为晚期胃食管腺癌的标准一线治疗。
 
附：英文原文
 
Title: Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer

Author: Shitara, Kohei, Ajani, Jaffer A., Moehler, Markus, Garrido, Marcelo, Gallardo, Carlos, Shen, Lin, Yamaguchi, Kensei, Wyrwicz, Lucjan, Skoczylas, Tomasz, Bragagnoli, Arinilda Campos, Liu, Tianshu, Tehfe, Mustapha, Elimova, Elena, Bruges, Ricardo, Zander, Thomas, de Azevedo, Sergio, Kowalyszyn, Ruben, Pazo-Cid, Roberto, Schenker, Michael, Cleary, James M., Yanez, Patricio, Feeney, Kynan, Karamouzis, Michalis V., Poulart, Valerie, Lei, Ming, Xiao, Hong, Kondo, Kaoru, Li, Mingshun, Janjigian, Yelena Y.

Issue&Volume: 2022-03-23

Abstract: 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 adenocarcinoma1,2,3,4. 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 trial5 (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 countries6. 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, respectively7,8,9,10,11. Treatment combining 1mg kg1 nivolumab with 3mg kg1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus 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 score≥5 (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.

DOI: 10.1038/s41586-022-04508-4

Source: https://www.nature.com/articles/s41586-022-04508-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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