Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR-1210), a novel anti-PD-1 antibody

Thorac Cancer. 2019 Jun;10(6):1395-1401. doi: 10.1111/1759-7714.13083. Epub 2019 Apr 24.

Abstract

Background: A small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors; however, reliable peripheral blood biomarkers for outcomes of anti-PD-1 immunotherapy in ESCC have not been identified.

Methods: The data of 43 patients in the ESCC cohort of a phase I trial at our center were retrospectively reviewed. All patients were administered intravenous camrelizumab (SHR-1210), a novel anti-PD-1 antibody, at doses of 60 mg, 200 mg, or 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. Associations between lactate dehydrogenase (LDH) and other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated.

Results: After median follow-up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression-free and overall survival rates were 2.0 and 8.0 months, respectively. Patients with an elevated baseline LDH had lower tumor response rates (P = 0.02) and shorter progression-free (P = 0.002) and overall (P < 0.0001) survival than patients with normal LDH levels. An increase in LDH levels during treatment was significantly associated with disease progression. Multivariate Cox analysis identified LDH (hazard ratio [HR] 0.18), CRP (HR 0.27), the number of organs involved (HR 0.31), absolute monocyte count (HR 0.33), and Eastern Cooperative Oncology Group performance status (HR 0.36) as independent prognostic factors.

Conclusions: Serum LDH, which is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients treated with anti-PD-1 therapy.

Keywords: Esophageal squamous cell carcinoma; immune checkpoint inhibitor; lactate dehydrogenase; markers; programmed cell death-1.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Disease Progression
  • Drug Administration Schedule
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Female
  • Humans
  • L-Lactate Dehydrogenase / blood*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • camrelizumab
  • C-Reactive Protein
  • L-Lactate Dehydrogenase