Perioperative tislelizumab with four cycles of neoadjuvant chemotherapy for resectable locally advanced esophageal squamous cell carcinoma: a phase 2 study

Front Immunol. 2024 Dec 2:15:1482005. doi: 10.3389/fimmu.2024.1482005. eCollection 2024.

Abstract

Background: The application of neoadjuvant immunotherapy in the treatment of esophageal cancer needs further exploration. This study aimed to investigate the safety and effectiveness of tislelizumab, an anti-PD-1 antibody, combined with chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (LA-ESCC).

Methods: In this phase II study, patients with clinical stages of II-IVA (T3-T4 and/or node positive) potentially resectable LA-ESCC were enrolled. Patients received neoadjuvant tislelizumab and chemotherapy every 3 weeks for 4 cycles before surgery and adjuvant tislelizumab for 9 months. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included R0 resection, disease free survival (DFS), adverse events (AE), and biomarkers for predicting efficacy.

Results: The study included 30 patients. 25 patients completed neoadjuvant chemoimmunotherapy and underwent surgery, 96% with R0 resection. The pCR and MPR rate was 44% and 52%. The 6-month and 1-year DFS rate was 100% and 75.3%. 43.3% patients experienced severe (grade 3-4) treatment-related adverse events (TRAEs) and 5 patients developed severe immune-related adverse events (irAEs). Further exploration found that a group of peripheral lymphocyte subsets increased significantly after 2 cycles of neoadjuvant therapy in patients who achieved pCR, suggesting the importance of dynamic monitoring of circulating lymphocyte.

Conclusions: The combination of perioperative tislelizumab and neoadjuvant chemotherapy has achieved an encouraging pCR rate and demonstrated a manageable safety profile in patients with potentially resectable ESCC.

Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2100043772.

Keywords: esophageal squamous cell carcinoma; immunotherapy; neoadjuvant chemotherapy; perioperative treatment; tislelizumab.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Esophageal Squamous Cell Carcinoma* / therapy
  • Esophagectomy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Neoplasm Staging
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • tislelizumab

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-A-215).