Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors. (May 2021)

• Record Type: Journal Article
• Authors: Liu, Jia; Itchins, Malinda; Nagrial, Adnan; Cooper, Wendy A.; De Silva, Madhawa; Barnet, Megan; Varikatt, Winny; Sivasubramaniam, Vanathi; Davis, Alexander; Gill, Anthony J.; Blinman, Prunella; Lee, Kenneth; Hui, Rina; Gao, Bo; Pavlakis, Nick; Clarke, Stephen; Lee, Jenny; Boyer, Michael; Kao, Steven
• Is Part Of: Lung cancer. Volume 155(2021)
• Page Start: 28
• Page End: 33
• Publication Date: 2021-05
• Subjects: EGFR mutated -- NSCLC -- Programmed death ligand 1 -- PD-L1 -- De novo resistance; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.03.004
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: PD-L1 as a biomarker in EGFR-mutant lung adenocarcinoma is controversial. High baseline PD-L1 expression was associated with shorter PFS and OS to EGFR TKI. PD-L1 expression was the most significant prognostic biomarker. Post-progression high PD-L1 was not associated with poor outcomes. Abstract: Objectives: Predictive biomarkers for poor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is an area of ongoing research. This multicentre retrospective study sought to determine the impact of programmed death-ligand 1 (PD-L1) tumour proportional score (TPS) on outcome in EGFR TKI treated patients. Materials and Methods: Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising EGFR mutation treated with first-line TKI at five metropolitan hospitals were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay. High PD-L1 expression was defined as TPS ≥ 50 %. Determinants of progression and survival hazards were modelled using Cox regression. Results: A total of 186 patients were included. Mean age was 67 years, 66 % were female and 54 % were Asian. Patients with high PD-L1 expression (n = 23; 12 %) had significantly shorter progression free survival (6.6 vs 13.0 months, hazard ratio (HR) 2.6 95 % CI 1.6–4.2, p < 0.0001) and overall survival (11.5 vs 32.9 months, HR 3.3, 95 % CI 1.9–5.7, p < 0.0001) compared to patients with PD-L1 low/negative tumours. This remained significant in multivariate analyses. High PD-L1 in post-TKI progression biopsies was not associated with poorer survival. Conclusion: In this large, real-world cohort of EGFR- mutant lung adenocarcinoma patients, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs and shorter survival, regardless of ethnicity.