BACKGROUND Perioperative chemo-immunotherapy shows variable outcomes in resectable gastric or gastro-oesophageal junction adenocarcinoma. 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. METHODS In this randomised, double-blind, multicentre phase 3 ASTRUM-006 study, patients were screened at 75 hospitals in China and Thailand. 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). 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. This study is registered with ClinicalTrials.gov, NCT04139135, and is ongoing. FINDINGS 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). 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 ratio 0·65 95% CI 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-treat population (NR vs 35·9 months; 0·73 95% CI 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. 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. Extended follow-up for the overall survival data is warranted to confirm a survival advantage of this perioperative strategy with a chemotherapy-sparing adjuvant component for this indication. FUNDING Shanghai Henlius Biotech.
Shen et al. (Mon,) studied this question.