Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2)

Nat Commun. 2022 Feb 14;13(1):857. doi: 10.1038/s41467-022-28408-3.

Abstract

This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.2 vs.6.2 months; P = 0.032; HR = 0.70; 95% CI, 0.50-0.97). Incidence of treatment-related adverse events of grade 3-5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1%). Patients with high T-cell receptor (TCR) clonality and low molecular tumor burden index (mTBI) showed the longest median OS (15.0 months). Patients with NLR < 3 at 6 weeks post-treatment had a significantly prolonged median OS (16.6 months) compared with NLR ≥ 3. The results demonstrate a significant improvement in OS of sintilimab compared to chemotherapy as second-line treatment for advanced or metastatic ESCC.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / mortality
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Irinotecan / therapeutic use
  • Male
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Progression-Free Survival
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell
  • Irinotecan
  • sintilimab
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT03116152