纳武利尤单抗联合化疗用于 HER2 阴性、未经治疗、不可切除、晚期或复发性胃/胃食管交界处癌患者：ATTRACTION-4 随机、双盲、安慰剂对照、3 期临床试验的 3 年随访结果。
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.
机构信息
Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.
出版信息
Gastric Cancer. 2024 Nov;27(6):1287-1301. doi: 10.1007/s10120-024-01535-0. Epub 2024 Aug 20.
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.
背景
纳武利尤单抗联合化疗现已成为 HER2 阴性、未经治疗、不可切除或复发性胃/胃食管交界处癌（晚期胃癌）的标准治疗方法，但临床试验的长期随访数据有限。
方法
ATTRACTION-4 是一项在日本、韩国和中国台湾开展的 3 期、双盲、安慰剂对照临床试验。患者被随机分配至纳武利尤单抗或安慰剂组，两组均联合医生选择的 SOX（替吉奥胶囊[S-1（替加氟、吉美嘧啶、奥替拉西钾）]联合奥沙利铂）或 CAPOX（卡培他滨联合奥沙利铂）治疗。我们报告了主要终点——中心评估的无进展生存期（PFS）和总生存期（OS），以及使用 3 年随访数据的 OS 里程碑分析。
结果
截至截止日期（2021 年 5 月 10 日），纳武利尤单抗联合化疗组的 359 例患者中有 17 例和安慰剂联合化疗组的 358 例患者中有 6 例仍在接受研究治疗。纳武利尤单抗联合化疗组的 PFS（中心评估）更长（中位 10.94 个月 vs. 8.48 个月；风险比 [HR]0.67，95%置信区间 [CI]0.55-0.82）。尽管两组的 OS 无差异（中位 17.45 个月 vs. 17.15 个月；HR0.89，95%CI0.75-1.05），但 OS 的里程碑分析，即在每个里程碑时间点（每月）计算 HR，随着时间的推移，纳武利尤单抗联合化疗组的 HR 逐渐更好。在纳武利尤单抗联合化疗组中，约 80%达到完全缓解的患者在 3 年时仍存活。纳武利尤单抗联合化疗未观察到新的安全性信号或主要晚期发生的与治疗相关的不良事件。
结论
ATTRACTION-4 的 3 年随访结果证实了纳武利尤单抗联合化疗在未经治疗的晚期胃癌患者中的长期临床获益和可管理的安全性。
试验注册
NCT02746796。
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