Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors

Jia Liu; Malinda Itchins; Adnan Nagrial; Wendy A Cooper; Madhawa De Silva; Megan Barnet; Winny Varikatt; Vanathi Sivasubramaniam; Alexander Davis; Anthony J Gill; Prunella Blinman; Kenneth Lee; Rina Hui; Bo Gao; Nick Pavlakis; Stephen Clarke; Jenny Lee; Michael Boyer; Steven Kao

doi:10.1016/j.lungcan.2021.03.004

Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors

Lung Cancer. 2021 May:155:28-33. doi: 10.1016/j.lungcan.2021.03.004. Epub 2021 Mar 9.

Authors

Jia Liu¹, Malinda Itchins², Adnan Nagrial³, Wendy A Cooper⁴, Madhawa De Silva⁵, Megan Barnet⁶, Winny Varikatt⁷, Vanathi Sivasubramaniam⁸, Alexander Davis⁹, Anthony J Gill¹⁰, Prunella Blinman¹¹, Kenneth Lee¹², Rina Hui¹³, Bo Gao¹⁴, Nick Pavlakis², Stephen Clarke¹⁵, Jenny Lee⁹, Michael Boyer¹⁶, Steven Kao¹⁷

Affiliations

¹ Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Children's Medical Research Institute, Westmead, NSW, Australia.
² Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
³ Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
⁴ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, NSW, Australia; Sydney School of Medicine, Western Sydney University, NSW, Australia.
⁵ Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
⁶ Kinghorn Cancer Centre, Darlinghurst, NSW, Australia; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁷ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia.
⁸ Sydpath, St Vincent's Hospital, Darlinghurst, NSW, Australia.
⁹ Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
¹⁰ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹¹ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Concord Repatriation General Hospital, Concord, NSW, Australia.
¹² Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Anatomical Pathology, NSW Health Pathology, Concord Repatriation General Hospital, Sydney, NSW, Australia.
¹³ Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
¹⁴ Crown Princess Mary Cancer Centre, Westmead, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia.
¹⁵ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹⁶ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
¹⁷ Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Chris O'Brien Lifehouse, Camperdown, NSW, Australia. Electronic address: steven.kao@lh.org.au.

PMID: 33721613
DOI: 10.1016/j.lungcan.2021.03.004

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.

Keywords: De novo resistance; EGFR mutated; NSCLC; PD-L1; Programmed death ligand 1.

Publication types

Multicenter Study

MeSH terms

Aged
B7-H1 Antigen* / genetics
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Drug Resistance, Neoplasm / genetics*
ErbB Receptors / genetics
Female
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Male
Mutation
Protein Kinase Inhibitors / therapeutic use
Retrospective Studies

Substances

B7-H1 Antigen
Protein Kinase Inhibitors
EGFR protein, human
ErbB Receptors