Impact of bowel movement condition on immune checkpoint inhibitor efficacy in patients with advanced non-small cell lung cancer

Thorac Cancer. 2019 Mar;10(3):526-532. doi: 10.1111/1759-7714.12969. Epub 2019 Jan 21.

Abstract

Background: Cancer immunotherapy is under development as a promising alternative strategy for treating advanced non-small cell lung cancer (NSCLC). However, the development of novel biomarkers to optimize the use of immune checkpoint inhibitors (ICIs) is still ongoing. Gut microbiota are known to regulate a host's immunity and are associated with the response to ICIs in melanoma. Therefore, we analyzed the association between ICI treatment efficacy and bowel movement condition in patients with NSCLC.

Methods: This retrospective study analyzed patients with advanced NSCLC who were treated with ICIs between December 2015 and March 2018 at University Hospital Kyoto Prefectural University of Medicine in Kyoto, Japan. The association between stool abnormalities and ICI efficacy was investigated. We defined patients with constipation or those who used a laxative as the stool abnormality group.

Results: We retrospectively enrolled 40 patients with advanced NSCLC who were treated with ICIs. The median age was 69.5 years; 20 patients had a stool abnormality and 20 patients did not. The disease control rates were lower in NSCLC patients with stool abnormalities than in those without stool abnormalities (20% vs. 77.8%, respectively; P = 0.0016). The time to treatment failure with ICI treatment was shorter in NSCLC patients with stool abnormalities compared with those without stool abnormalities (P = 0.003; odds ratio, 3.09; 95% confidence interval 1.41-6.78).

Conclusion: Stool abnormality might be a predictive biomarker for the clinical benefit of ICI treatment in patients with NSCLC. Further investigations are warranted to validate our findings.

Keywords: Biomarker; bowel movement condition; immunotherapy; non-small cell lung cancer; retrospective study.

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • C-Reactive Protein / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / microbiology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Constipation / chemically induced
  • Constipation / epidemiology*
  • Constipation / microbiology
  • Constipation / pathology
  • Fecal Incontinence / chemically induced
  • Fecal Incontinence / microbiology
  • Fecal Incontinence / pathology
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology
  • Genes, cdc / drug effects*
  • Humans
  • Immunity / drug effects
  • Immunity / immunology
  • Immunotherapy / adverse effects*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Retrospective Studies

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • C-Reactive Protein