PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study

Sci Rep. 2021 Aug 19;11(1):16892. doi: 10.1038/s41598-021-96486-2.

Abstract

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001-2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ([Formula: see text] 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan-Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors-51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8-17.9) and 13.4 (95% CI = 9.5-16.3) in PD-L1+ and PD-L1- tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74-1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63-1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39-0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / metabolism*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cohort Studies
  • Confidence Intervals
  • Denmark
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mutation / genetics*
  • Neoplasm Staging
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • KRAS protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)