Nivolumab联合化疗治疗HER2阴性、既往未经治疗、无法切除、晚期或复发性胃癌/胃食管交界癌患者:ATTRACTION-4 随机、双盲、安慰剂对照 3 期试验的 3 年随访。

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gastric Cancer Pub Date : 2024-11-01 Epub Date: 2024-08-20 DOI:10.1007/s10120-024-01535-0
Narikazu Boku, Takeshi Omori, Kohei Shitara, Shinichi Sakuramoto, Kensei Yamaguchi, Ken Kato, Shigenori Kadowaki, Kunihiro Tsuji, Min-Hee Ryu, Do-Youn Oh, Sang Cheul Oh, Sun Young Rha, Keun-Wook Lee, Ik-Joo Chung, Sun Jin Sym, Li-Tzong Chen, Jen-Shi Chen, Li-Yuan Bai, Takashi Nakada, Shunsuke Hagihara, Reina Makino, Eiji Nishiyama, Yoon-Koo Kang
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引用次数: 0

摘要

背景:Nivolumab+化疗是目前治疗HER2阴性、既往未经治疗、不可切除或复发胃癌/胃食管交界处癌(晚期胃癌)的标准疗法,但临床试验的长期随访数据有限:ATTRACTON-4是一项在日本、韩国和台湾进行的3期双盲安慰剂对照试验。患者随机接受 nivolumab 或安慰剂治疗,两者均结合医生选择的 SOX(口服 S-1[替加氟-吉米拉西啶-奥曲铂钾]+ 奥沙利铂)或 CAPOX(卡培他滨+ 奥沙利铂)治疗。我们报告了主要终点--集中评估的无进展生存期(PFS)和总生存期(OS)--以及利用3年随访数据对存活患者的OS进行的标志性分析:截止日期(2021年5月10日),nivolumab+化疗组有17/359名患者继续接受研究治疗,安慰剂+化疗组有6/358名患者继续接受研究治疗。nivolumab+化疗组的PFS(集中评估)更长(中位10.94个月对8.48个月;危险比[HR]0.67,95%置信区间[CI]0.55-0.82)。虽然两组患者的OS没有差异(中位17.45个月对17.15个月;HR 0.89,95% CI 0.75-1.05),但对OS进行地标分析,计算每个地标时间点(每个月)的HR,结果显示,随着时间的推移,nivolumab+化疗组的OS在数字上越来越好。在nivolumab+化疗组中,约80%获得完全应答的患者在3年后仍然存活。nivolumab+化疗未发现新的安全信号或重大的晚发选择性治疗相关不良事件:ATTRACTION-4的3年随访证实了nivolumab+化疗对既往未经治疗的晚期胃癌患者的长期临床获益和可控安全性:NCT02746796。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial.

Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial.

Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited.

Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur-gimeracil-oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints-centrally assessed progression-free survival (PFS) and overall survival (OS)-and landmark analyses of OS among patients alive using 3-year follow-up data.

Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55-0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75-1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy.

Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer.

Trial registration: NCT02746796.

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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
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