Mutation-guided chemotherapy-free strategy in first-line immunotherapy for low PD-L1-expressing non-squamous NSCLC

Autor: Hui Li, Liang Zhang, Yu Xu, Jingjing Liu, Guoqiang Wang, Ying Cheng, Shangli Cai, Xinyue Wang, Peng Cui, Shaowei Lan
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 12, Iss 11 (2024)
Druh dokumentu: article
ISSN: 2051-1426
DOI: 10.1136/jitc-2024-009693
Popis: Background The necessity of platinum-doublet chemotherapy in first-line immunotherapy for non-squamous non-small cell lung cancer (nsqNSCLC) with programmed death-ligand 1 (PD-L1) expression on less than 50% of tumor cells remains poorly investigated. Biomarkers predicting this necessity can guide chemotherapy-free treatment to minimize unnecessary toxicity.Methods Treated with immune checkpoint inhibitor monotherapy (ICI-mono), chemotherapy, or combination (ICI-chemo), 790 low PD-L1-expressing nsqNSCLCs (in-house: n=83; public: n=707) were analyzed for development and validation of the interaction score for additional chemotherapy (ISAC). Transcriptomic (public, n=11) and multiplex immunofluorescence data (in-house, n=100) were analyzed to evaluate the immune microenvironment.Results ICI-chemo, compared with ICI-mono, tended to prolong progression-free survival (PFS; HR=0.72, p=0.004) and overall survival (OS; HR=0.77, p=0.071) as first-line therapy in low PD-L1-expressing nsqNSCLCs. The added value of chemotherapy was observed in the ISAC-low subgroup (PFS: HR=0.48, p
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