Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study
Mené sur 588 patients atteints d'un cancer gastrique ou de la jonction oesogastrique surexprimant PD-L1 (âge médian : 61 ans ; durée médiane de suivi : 42,7 mois), cet essai multicentrique de phase III évalue l'efficacité, du point de vue de la survie sans événement, et la toxicité de l'ajout du serplumimab à une chimiothérapie néoadjuvante de type SOX (S-1 et oxaliplatine) suivie d'un traitement adjuvant par serplimumab ou SOX
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.
The Lancet , résumé, 2026