Perioperative tislelizumab plus chemotherapy for locally advanced gastroesophageal junction adenocarcinoma (NEOSUMMIT-03): a prospective, nonrandomized, open-label, phase 2 trial

Abstract

This prospective, nonrandomized, open-label phase 2 trial (Chinese Clinical Trial Registry, ChiCTR2200061906) aimed to evaluate the effectiveness of adding the PD-1 antibody tislelizumab to perioperative chemotherapy in patients with locally advanced gastroesophageal junction adenocarcinoma (GEJA). This study enrolled patients with GEJA clinically staged as cT3-4aNanyM0 or cT1-2N+M0 from October 2022 to June 2023. Eligible patients were administered three preoperative and five postoperative 3-week cycles of treatment with PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. Thirty-two patients were enrolled. The median age was 60 years (range: 28-74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 93.8% (30/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. The R0 resection rate was 96.9% (31/32). MPR, pathological complete response (pCR) of primary tumors and ypT0N0 rates were 50.0% (16/32, 95% CI: 31.9-68.1%), 28.1% (9/32, 95% CI: 13.7-46.7%) and 25.0% (8/32, 95% CI: 11.5-43.4%), respectively. The surgical morbidity rate was 15.6% (5/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment periods, the rate of treatment-related grade 3-4 adverse events was 31.2% (10/32). At the date of 7^th Jan 2025, 8 (25.0%) patients occurred recurrence. Therefore, perioperative tislelizumab plus chemotherapy demonstrated significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJA.

Fig. 1

CONSORT diagram

Fig. 2

Tumor response to neoadjuvant therapy and follow-up. a Waterfall plot of tumor regression rates after neoadjuvant therapy based on pathology. b Swimmer plot showing treatment events and follow-up in the population of all included patients. PD-L1, programmed cell death-ligand 1, CPS, combined positive score; EBV, Epstein-Barr virus; MPR, major pathological response

Fig. 3

Kaplan-Meier plots for (a) OS and (b) EFS. OS, overall survival; EFS, event-free survival

Fig. 4

Histopathological tumor regression rates by clinicopathological characteristics. a MPR; b ypT0N0. MPR major pathological response, PD-L1 programmed cell death-ligand 1, CPS combined positive score

Fig. 5

Immune cell landscape of patients at baseline and after neoadjuvant treatment. a, b Heatmaps depicting 28 subpopulations of tumor-infiltrating lymphocytes at baseline and after neoadjuvant treatment in patients who achieved a MPR (a, top panel) and those who did not (b, bottom panel); (c–f) Paired analysis of Treg (c), γδT (d), neutrophil (e) and eosinophils (f) cell infiltration at baseline and after neoadjuvant treatment in patients who achieved a MPR (left panel) and those who did not (right panel). MPR major pathological response. Wilcoxon signed-rank test