Biomarker expression and survival in patients with non-small cell lung cancer receiving adjuvant chemotherapy in Denmark

PLoS One. 2023 Apr 11;18(4):e0284037. doi: 10.1371/journal.pone.0284037. eCollection 2023.

Abstract

Introduction: Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy.

Methods: Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001-2012) were retrieved from Danish population-based registries. Tumor tissue samples were tested for PD-L1 expression using VENTANA PD-L1 (SP263) Assay in tumor cells (TC) at ≥25% cutoff and immune cells (IC) at ≥1% and ≥25% cutoffs. KRAS and EGFR mutations were tested using PCR-based assays. Follow-up began 120 days after diagnosis until death/emigration/January 1, 2015, whichever came first. Using Cox proportional hazard regression, hazard ratios (HRs) were computed for overall survival (OS) for each biomarker, adjusting for age, sex, histology, comorbidities, and tissue specimen age.

Results: Among 391 patients identified, 40.4% had stage IIIA disease, 49.9% stage II, and 8.7% stage IB. PD-L1-TC was observed in 38% of patients, EGFR mutations in 4%, and KRAS mutations in 29%. KRAS mutations were more frequent among patients with PD-L1 TC≥25% versus TC<25% (37% versus 24%). OS was not associated with PD-L1 TC≥25% versus TC<25% (stage II: adjusted HR = 1.15 [95% confidence interval: 0.66-2.01]; stage IIIA: 0.72 [0.44-1.19]). No significant association was observed with OS and PD-L1-IC ≥1% and ≥25%. EGFR and KRAS mutations were not associated with a prognostic impact.

Conclusion: A prognostic impact for NSCLC patients receiving adjuvant chemotherapy was not associated with PD-L1 expression, or with EGFR and KRAS mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Denmark
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms* / pathology
  • Proto-Oncogene Proteins p21(ras) / metabolism

Substances

  • B7-H1 Antigen
  • Proto-Oncogene Proteins p21(ras)
  • Biomarkers, Tumor
  • ErbB Receptors

Grants and funding

This work was funded by AstraZeneca research grants to EpidStat Institute (now EpidStrategies) to manage and administer the work. Aarhus University, Denmark, received funds from EpidStat Institute to conduct the work. The funder provided support in the form of salaries for authors Tapashi Dalvi, Jill Walker, Anita Midha, Norah Shire, Anders Mellemgaard, and Anne Marie Boothman. The specific roles of these authors are articulated in the ‘author contributions’ section. The authors had the final responsibility for the decision to submit the manuscript for publication. The funder was involved in the study design and preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.