Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study.

We evaluated the efficacy and safety of neoadjuvant serplulimab with S-1 plus oxaliplatin (SOX) chemotherapy followed by adjuvant serplulimab versus neoadjuvant placebo plus SOX followed by adjuvant SOX in patients with PD-L1-positive, locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma.

我们评估了在PD-L1阳性、局部晚期、可切除的胃癌或胃食管交界处腺癌患者中，新辅助使用serplulimab联合S-1加奥沙利铂(SOX)化疗后进行辅助serplulimab治疗，与新辅助使用安慰剂加SOX化疗后进行辅助SOX治疗的疗效和安全性。

Methods

In this randomised, double-blind, multicentre phase 3 ASTRUM-006 study, patients were screened at 75 hospitals in China and Thailand.

在这项随机、双盲、多中心的ASTRUM-006期III临床研究中，患者在中国和泰国的75家医院进行了筛查。

Eligible patients aged 18-70 years with PD-L1 combined positive score (CPS) ≥5, resectable gastric or gastro-oesophageal junction adenocarcinoma were randomly assigned 1:1 to neoadjuvant serplulimab or placebo (intravenous; 4·5 mg/kg) plus SOX chemotherapy (intravenous oxaliplatin 130 mg/m2 on day 1, and oral S1 40-60 mg twice daily on days 1-14) for three cycles (cycle length 21 days), followed by adjuvant serplulimab (up to 17 cycles; serplulimab group) or SOX (five cycles; placebo group).

符合条件的18-70岁患者，PD-L1联合阳性评分（CPS）≥5，可切除的胃或胃食管交界处腺癌患者按1:1的比例随机分配接受新辅助serplulimab或安慰剂（静脉注射；4.5 mg/kg）加上SOX化疗方案（静脉注射奥沙利铂130 mg/m2，第1天，口服S1 40-60 mg，每日两次，第1-14天）治疗三个周期（每个周期21天），随后接受辅助serplulimab治疗（最多17个周期；serplulimab组）或SOX治疗（五个周期；安慰剂组）。

The primary endpoint was investigator-assessed event-free survival (defined as the time from randomisation to the occurrence of progressive disease or local or distant recurrence, other new malignancies, or death), with efficacy first evaluated in PD-L1 CPS ≥10, then in the intention-to-treat(CPS ≥5) population.

主要终点是研究者评估的无事件生存期（定义为从随机分组到疾病进展或局部或远处复发、其他新发恶性肿瘤或死亡的时间），首先在PD-L1 CPS≥10的患者中评估疗效，然后在意向治疗（CPS≥5）人群中评估。

This study is registered with ClinicalTrials.gov, NCT04139135, and is ongoing.

该研究已在ClinicalTrials.gov上注册，注册号为NCT04139135，目前仍在进行中。

Results

Between Nov 26, 2019, and April 19, 2024, 1646 patients were screened, of whom 588 patients (median age 61·0 years [IQR 55-66]; 124 [21%] female and 464 [79%] male) at 57 hospitals in China were randomly assigned to the serplulimab group (n=292) or placebo group (n=296).

在2019年11月26日至2024年4月19日期间，共筛选了1646名患者，其中588名患者（中位年龄61.0岁 [四分位数间距55-66]；女性124名[21%]，男性464名[79%]）在中国的57家医院随机分配到serplulimab组（n=292）或安慰剂组（n=296）。

With a median follow-up duration of 42·7 months (IQR 24·3-53·6), median event-free survival was significantly longer with serplulimab than with placebo in the PD-L1 CPS ≥10 population (not reached [NR] vs 42·0 months; hazard ratio0·65 [95% CI 0·47-0·90]; p=0·0082).

在中位随访时间为42.7个月（四分位数间距24.3-53.6）的情况下，PD-L1 CPS ≥10人群中，serplulimab组的中位无事件生存期显著长于安慰剂组（未达到[NR] vs 42.0个月；风险比为0.65 [95%置信区间0.47-0.90]；p=0.0082）。

With a median follow-up of 35·9 months (IQR 23·5-49·4), median event-free survival was also significantly longer with serplulimab than with placebo in the intention-to-treatpopulation (NR vs 35·9 months; 0·73 [95% CI 0·56-0·94]; p=0·015).

在中位随访时间为35.9个月（四分位数间距23.5-49.4）的情况下，意向治疗人群中，与安慰剂相比，serplulimab的无事件生存期中位数也显著更长（未达到vs 35.9个月；0.73 [95% 置信区间 0.56-0.94]；p=0.015）。

Grade 3 or worse treatment-related adverse events occurred in 136 (47%) patients in the serplulimab group and 172 (59%) patients in the placebo group; 19 (7%) and 31 (11%) patients in the respective groups discontinued treatment due to treatment-related adverse events.

在serplulimab组中有136名（47%）患者和在安慰剂组中有172名（59%）患者发生了3级或更严重的与治疗相关的不良事件；相应地，有19名（7%）和31名（11%）患者因与治疗相关的不良事件而停止治疗。

interpretation

Neoadjuvant serplulimab plus SOX followed by adjuvant serplulimab significantly improved event-free survival and demonstrated a better safety profile compared with neoadjuvant and adjuvant SOX in PD-L1-positive, resectable gastric or gastro-oesophageal junction adenocarcinoma.

新辅助serplulimab联合SOX方案后行辅助serplulimab治疗，与新辅助及辅助SOX方案相比，显著改善了PD-L1阳性可切除胃癌或胃食管交界处腺癌患者的无事件生存期，并显示出更好的安全性。

Extended follow-up for the overall survivaldata is warranted to confirm a survival advantage of this perioperative strategy with a chemotherapy-sparing adjuvant component for this indication.

对于这种化疗辅助成分较少的围手术期策略，有必要进行总生存数据的长期随访，以确认其在这一适应症上的生存优势。

funding

Shanghai Henlius Biotech.

上海复宏汉霖生物技术有限公司