A Retrospective Evaluation of Pd-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (Replica)

Abstract

BackgroundImmune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumour and nodal metastases in the surgical setting are sparse.MethodsWe assessed PD-L1 expression in paired primary tumour and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess inter-tumour heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored.ResultsUsing PD-L1 expression categories of <1%, 1-49% and ≥50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman’s coefficient 0.7). 46% of early-stage primary tumours expressed PD-L1, although only 11% demonstrated a high (>50%) level. It was more common for PD-L1 expression to be higher in the primary tumour than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival.ConclusionOur study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.

Note:
Funding Declaration: This research was sponsored and funded by MSD UK Limited, London, UK.

Conflict of Interests: AB is a consultant for Intuitive and Becton, Dickinson, and Company (BD). DJH has received honoraria/speaker fees from Bristol Myers Squibb, Pfizer and Servier, transport/accommodation grants from Bristol Myers Squibb, Pfizer, Servier, Roche and Nanomab Technology (UK) Limited, research funding via institute from Nanomab, and is an executive committee member of the Association of Cancer Physicians (UK). DJ received support to attend educational conferences from BMS, Pfizer, EUSA Pharma, Ipsen, Janssen, MSD. Speaking fees: Astrazeneca, Pfizer, Janssen, Bayer. All other authors have no declarations.

Ethical Approval: The study obtained the required ethical approvals from UK Research Ethics Committee (IRAS number 228790).

Keywords: Early-stage non-small cell lung cancer, PD-L1 expression, Immunotherapy, inter-tumoural heterogeneity