In a Chinese phase III study (ASTRUM-006) reported in The Lancet, Shen et al found that neoadjuvant serplulimab plus S-1/oxaliplatin (SOX) followed by adjuvant serplulimab improved event-free survival vs neoadjuvant and adjuvant SOX in patients with PD-L1–positive, resectable gastric or gastroesophageal junction adenocarcinoma.
Study Details
The multicenter double-blind trial enrolled 588 patients with a PD-L1 combined positive score (CPS) of ≥ 5. They were randomly assigned between November 2019 and April 2024 to receive neoadjuvant serplulimab at 4.5 mg/kg (n = 292) or placebo (n = 296) plus SOX (oxaliplatin at 130 mg/m² on day 1 and S-1 40–60 mg twice daily on days 1–14) for three 21-day cycles, 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, with efficacy first evaluated in the PD-L1 CPS ≥ 10 population and then in the CPS ≥ 5 population.
Key Findings
With a median follow-up of 42.7 months (interquartile range [IQR] = 24.3–53.6 months), median event-free survival in the CPS ≥ 10 population was not reached in the serplulimab group vs 42.0 months in the placebo group (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.47–0.90, P = .0082).
With a median follow-up of 35.9 months (IQR = 23.5–49.4 months), median event-free survival in the CPS ≥ 5 population was not reached in the serplulimab group vs 35.9 months in the placebo group (HR = 0.73, 95% CI = 0.56–0.94, P = .015).
Grade ≥ 3 treatment-related adverse events occurred in 47% of patients in the serplulimab group and 59% of the placebo group; the most common event in both groups was decreased platelets (17% vs 24%). Treatment-related adverse events led to discontinuation of treatment in 7% of the serplulimab group and 11% of the placebo group.
The investigators concluded: “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 gastroesophageal 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.”
Lin Shen, MD, and Jiafu Ji, MD, of State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Peking University Cancer Hospital & Institute, Beijing, are the corresponding authors for The Lancet article.
DISCLOSURE: The study was funded by Shanghai Henlius Biotech. For full disclosures of the study authors, visit thelancet.com.
