Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study

Emily Susannah Mander, Christopher Brian Merrick, Hugh Adam Nicholson, Hannah Kate Lord, Michelle Jane Ferguson, Gillian Smith (Lead / Corresponding author)

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    Abstract

    OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.

    AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy.

    METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status.

    RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS.

    CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.

    Original languageEnglish
    Article numbere076715
    Number of pages10
    JournalBMJ Open
    Volume13
    Issue number11
    Early online date21 Nov 2023
    DOIs
    Publication statusPublished - 21 Nov 2023

    Keywords

    • Humans
    • Carcinoma, Non-Small-Cell Lung/drug therapy
    • Lung Neoplasms/drug therapy
    • B7-H1 Antigen
    • Retrospective Studies
    • State Medicine
    • United Kingdom
    • Respiratory tract tumours
    • ONCOLOGY
    • Clinical Decision-Making
    • RADIOTHERAPY
    • CHEMOTHERAPY

    ASJC Scopus subject areas

    • General Medicine

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