Induction Therapy of Tislelizumab Combined with Cisplatin and 5-Fluorouracil and Subsequent Conversion Surgery in Patients with Unresectable Advanced Esophageal Squamous Cell Carcinoma: A Phase 2, Single Center Study

Ann Surg Oncol. 2024 Dec;31(13):9321-9331. doi: 10.1245/s10434-024-16033-x. Epub 2024 Aug 23.

Abstract

Background: This study reported the safety and efficacy of a phase 2, open-label, single-arm, exploratory clinical trial of induction immunochemotherapy in patients with initially unresectable advanced esophageal squamous cell carcinoma (ESCC).

Patients and methods: Patients underwent three cycles of induction therapy with tislelizumab, cisplatin, and 5-fluorouracil. The primary endpoints were the safety, major pathological response (MPR), and pathological complete response (pCR). Secondary endpoints included the R0 resection rate, disease-free survival (DFS), and overall survival (OS). Genomic data and immune microenvironment data were analyzed exploratively.

Results: The treatment was safe, with a grade 3 or higher adverse event rate of 14.9% (7/47). Of the total 47 patients enrolled in the study, 19 (40.4%) achieved MPR, 12 (25.5%) achieved pCR, 4 (8.5%) achieved complete clinical response (cCR) and declined surgery, and 23 (48.94%) underwent successful resection. Median follow-up was 18 months, with a median DFS of 24 months, a median OS of 36 months. A high tumor mutation burden was associated with a better prognosis for patients who underwent surgery. Patients who achieved pCR had higher levels of immune cell infiltration and a greater proportion and concentration of tertiary lymphoid structures compared with those who experienced a major pathological response.

Conclusions: Tislelizumab combined with chemotherapy is effective for ESCC, yielding high cCR, pCR, surgical conversion, and R0 resection rates, and tolerable adverse events.

Trial registration: NCT05469061.

Keywords: ESCC; Immunochemotherapy; Induction therapy; Tislelizumab; Tumor immune microenvironment.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Cisplatin* / administration & dosage
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / surgery
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Esophageal Squamous Cell Carcinoma* / surgery
  • Esophagectomy
  • Female
  • Fluorouracil* / administration & dosage
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy*
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate

Substances

  • Cisplatin
  • Fluorouracil
  • Antibodies, Monoclonal, Humanized
  • tislelizumab

Associated data

  • ClinicalTrials.gov/NCT05469061