Highlights
- •Immune-checkpoint inhibitors (ICIs)are becoming a standard in early non-small cell lung cancer but do not benefit all patients.
- •Programmed death-ligand 1 expression and tumour mutational burden are the better-documented biomarkers.
- •Patients with epidermal growth factor receptor, Serine/Threonine Kinase 11 orKelch-like ECH-associated protein 1 alterations yield poor benefit from ICIs.
- •Emerging biomarkers include TCR clonality, microbiota and blood-based ratios.
- •Circulating tumour DNA is a reliable tool to evaluate disease burden following surgery or ICIs.
Abstract
Immunotherapy with immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 or programmed death-ligand 1 has revolutionised the treatment of advanced non-small cell lung cancer (NSCLC) and
has been investigated in early NSCLC, alone or in combination with chemotherapy, anti-CTLA-4
antibodies and radiotherapy. Although more mature data are needed before setting a
change of paradigm in early stages, reports of pathological response rates and disease-free
survival are promising, especially with neoadjuvant multimodality approaches. Nevertheless,
major pathological response rates for neoadjuvant anti-PD-(L)1 monotherapy rarely
exceed 40%, and biomarkers for characterising patients who may benefit the most from
ICIs are lacking. These biomarkers have a distinct value from the metastatic setting,
with highly different tumour biologies. Among the most investigated so far in this
context, programmed death-ligand 1 expression and, to a lesser extent, tumour mutational burden seem to correlate better
with higher pathological response rates and survival. Epidermal growth factor receptor, Serine/Threonine Kinase 11and Kelch-like ECH-associated protein 1 mutations rise as essential determinations for the treatment selection in early-stage
NSCLC. Emerging and promising approaches comprise evaluation of blood-based ratios,
microbiota, and baseline intratumoural TCR clonality. Circulating tumour DNA will
be of great help in the near future when selecting best candidates for adjuvant ICIs,
monitoring the tumour response to the neoadjuvant treatment in order to improve the
rates of complete resections in the early stage.
Keywords
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Article info
Publication history
Published online: February 17, 2023
Accepted:
January 30,
2023
Received:
December 9,
2022
Identification
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© 2023 Elsevier Ltd. All rights reserved.
