Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial.

We aimed to examine its effect on overall survival.

我们旨在检查其对总生存期的影响。

Methods

MATTERHORN is a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial that took place in 147 medical centres in 20 countries (representing Asia, Europe, North America, and South America).

MATTERHORN是一项全球性的随机、双盲、安慰剂对照、多中心的3期临床试验，涉及20个国家的147个医疗中心（代表亚洲、欧洲、北美和南美）。

Adults with histologically documented resectable gastric or gastro-oesophageal junction adenocarcinoma (eligible for radical surgery; stage II-IVa) not previously treated with anticancer therapy were eligible.

符合入组条件的成年人包括有组织学证实的可切除胃癌或胃食管交界处腺癌（适合进行根治性手术；II-IVa期）且之前未接受过抗癌治疗的患者。

Participants were randomly assigned (1:1) to perioperative durvalumab plus FLOT or placebo plus FLOT.

参与者被随机分配（1:1）接受围手术期durvalumab加FLOT或安慰剂加FLOT。

Blocked randomisation (unique randomisation number via an interactive response technology system and randomisation and trial supply management system) was stratified by geographical region, clinical lymph node status, and PD-L1 expression.

采用分块随机化（通过交互式响应技术系统和随机化及试验供应管理系统获得唯一的随机化编号）并按地理区域、临床淋巴结状态和PD-L1表达情况进行分层。

Participants were centrally assigned using the interactive response technology system and randomisation and trial supply management system.

参与者通过交互式响应技术系统和随机化及试验供应管理系统进行中心分配。

Participants received durvalumab 1500 mg or placebo intravenously every 4 weeks on day 1 of each cycle plus FLOT intravenously every 2 weeks on days 1 and 15 of each cycle for four cycles (two neoadjuvant and two adjuvant), followed by durvalumab 1500 mg or placebo intravenously every 4 weeks on day 1 of each cycle for ten additional cycles.

参与者接受durvalumab 1500 mg或安慰剂静脉注射，每4周一次，在每个周期的第1天进行，加上FLOT静脉注射，每2周一次，在每个周期的第1天和第15天进行，共四个周期（两个新辅助和两个辅助），随后在每个周期的第1天接受durvalumab 1500 mg或安慰剂静脉注射，每4周一次，再进行额外的十个周期。

Participants, investigators, and those assessing outcomes were masked.

参与者、研究人员和评估结果的人员均被设盲。

The previously reported primary outcome was event-free survival; overall survivalin the intention-to-treatpopulation was a key secondary endpoint and is the main endpoint reported here.

先前报告的主要结果是无事件生存期；意向治疗人群中的总生存期是一个关键的次要终点，并且是这里报告的主要终点。

Safety data were collected throughout treatment and the follow-up period (up to and including 90 days after the last dose of the trial drug) and were analysed in participants who received at least one dose of trial treatment; these data were reported previously and are summarised here.

安全数据在治疗期间和随访期间（包括最后一次试验药物剂量后的90天内）收集，并对至少接受一次试验治疗的参与者进行了分析；这些数据之前已经报告过，并在这里进行了总结。

MATTERHORN is closed to recruitment but is ongoing and registered with ClinicalTrials.gov (NCT04592913).

MATTERHORN已经停止招募，但仍在进行中，并已在ClinicalTrials.gov注册（NCT04592913）。

Results

From Nov 17, 2020, to Sept 2, 2022, 1258 participants were enrolled and 948 were randomly assigned; 474 were randomly assigned to durvalumab and 474 to placebo.

从2020年11月17日到2022年9月2日，共有1258名参与者被纳入研究，948名被随机分配；474名被随机分配到durvalumab组，474名被随机分配到安慰剂组。

In a total of 948 participants, the median age was 62 years (IQR 54-68), 682 (72%) were male, and 266 (28%) were female.

在948名参与者中，中位年龄为62岁（四分位数间距54-68），682名（72%）为男性，266名（28%）为女性。

Overall survivalsignificantly improved in the durvalumab versus placebo group (hazard ratio0·78, 95% CI 0·63-0·96; p=0·021; significance threshold p<0·0499).

与安慰剂组相比，durvalumab组的总生存期显著改善（风险比0·78，95%置信区间0·63-0·96；p=0·021；显著性阈值p<0·0499）。

Adverse events with the outcome of death possibly related to any trial treatment occurred in 6 (1%) of 475 participants in the durvalumab group and 2 (<1%) of 469 participants in the placebo group.

可能与任何试验治疗相关的死亡不良事件发生在durvalumab组的475名参与者中的6名（1%）和安慰剂组的469名参与者中的2名（<1%）。

interpretation

Perioperative durvalumab plus FLOT improved overall survivalversus placebo plus FLOT and is a new standard treatment option for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma.

围手术期使用durvalumab联合FLOT方案相较于安慰剂联合FLOT方案能显著改善可切除性胃癌或胃食管交界处腺癌患者的总生存期，成为这类患者的新的标准治疗选择。

funding

AstraZeneca.

阿斯利康制药公司。