Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery.

在化疗放疗和手术后，辅助使用纳武利尤单抗在食管/食管胃交界处癌和残留病理疾病中是有效的。

Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer.

免疫检查点抑制在晚期胃食管癌中显示出疗效。

We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection.

我们假设，在接受新辅助化疗和手术切除后的胃食管腺癌高危（ypN+和/或R1）患者中，纳武利尤单抗/伊匹木单抗比辅助化疗更有效。

patients_and_methods

VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence.

VESTIGE 是一项学术性的国际多中心开放标签随机II期试验，评估了在高复发风险的胃食管腺癌中，辅助性纳武单抗/伊匹木单抗与化疗的疗效。

Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year.

患者按1:1的比例随机接受标准辅助化疗（与新辅助化疗相同方案）或每2周静脉注射纳武单抗3 mg/kg，以及每6周静脉注射伊匹木单抗1 mg/kg，持续1年。

Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery.

主要纳入标准包括接受新辅助化疗加手术后ypN+和/或R1状态。

The primary endpoint was disease-free survival in the intent-to-treat population.

主要终点是在意向治疗人群中无病生存。

Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

次要终点包括总生存、局部区域和远处失败率，以及根据国家癌症研究所不良事件通用术语标准v5.0的安全性评估。

Results

The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility.

独立数据监测委员会在2022年6月审查了计划中的240名患者中的189名患者的数据，并建议因无效而停止招募。

At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy).

在最终分析时，195名患者（98名接受纳武单抗/伊匹木单抗治疗和97名接受化疗）的中位随访时间为25.3个月。

Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval(CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio1.55 (95% CI 1.07-2.25, one-sided P = 0.99).

纳武单抗/伊匹木单抗组的中位无病生存期为11.4个月[95%置信区间（CI）8.4-16.8个月]，而化疗组为20.8个月（95% CI 15.0-29.9个月），风险比为1.55（95% CI 1.07-2.25，单侧P = 0.99）。

The 12-month disease-free survival rates were 47.1% and 64.0%, respectively.

12个月无病生存率分别为47.1%和64.0%。

There were no toxicity concerns or excess early discontinuations.

没有出现毒性问题或过早停药的情况。

Conclusions

Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.

在新辅助化疗和手术后，对于ypN+和/或R1胃食管腺癌患者，与化疗相比，纳武单抗/伊匹木单抗并未改善无病生存期。