Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial

Nat Commun. 2024 Aug 20;15(1):7116. doi: 10.1038/s41467-024-51105-2.

Abstract

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8-not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4-15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7-63.5) and 69.7% (95% CI: 55.7-87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / therapeutic use
  • Chemoradiotherapy / methods
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / radiotherapy
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Esophageal Squamous Cell Carcinoma* / radiotherapy
  • Esophageal Squamous Cell Carcinoma* / therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / therapeutic use
  • Progression-Free Survival

Substances

  • Antibodies, Monoclonal, Humanized
  • toripalimab
  • Paclitaxel
  • Carboplatin