A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project

Lung Cancer. 2019 May;131:95-103. doi: 10.1016/j.lungcan.2019.03.012. Epub 2019 Mar 15.

Abstract

Introduction: The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis.

Methods: PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining.

Results: PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas.

Conclusion: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

Keywords: Non-small cell lung cancer; PD-L1.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diagnosis
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cohort Studies
  • Europe
  • Follow-Up Studies
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • MET protein, human
  • Proto-Oncogene Proteins c-met