ArticleJournal for immunotherapy of cancer2024
Mutation-guided chemotherapy-free strategy in first-line immunotherapy for low PD-L1-expressing non-squamous NSCLC.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Somatic copy number alterations profiling in non-small cell lung cancer and their correlation with clinical efficacy in first-line treatment.Genome medicine · 2026Article
- TGFBI deficiency facilitates tumor associated macrophages M2 polarization and angiogenesis to promote pancreatic neuroendocrine neoplasms progression.Cancer cell international · 2026Article
- Biomarkers and ImmuneScores in lung cancer: predictive insights for immunotherapy and combination treatment strategies.Biological procedures online · 2025Review
- Tumor microenvironment-driven resistance to immunotherapy in non-small cell lung cancer: strategies for Cold-to-Hot tumor transformation.Cancer drug resistance (Alhambra, Calif.) · 2025Review
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Authors and funding
10 authors.
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Abstract
backgroundThe 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.
methodsTreated 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.
resultsICI-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<0.001; OS: HR=0.53, p=0.001) rather than the ISAC-high subgroup (PFS: HR=1.08, p=0.65; OS: HR=1.14, p=0.56). This predictive utility was independent of tumor mutational burden and PD-L1 expression, indicated by subgroup and multivariable analyses. A high ISAC was associated with adaptive immune resistance reflected by more proinflammatory (eg, CD8
conclusionA high ISAC was identified as a significant predictor for virtually no added value of platinum-doublet chemotherapy for first-line ICI treatment in low PD-L1-expressing nsqNSCLC. Our findings may help refine personalized therapeutic strategies for nsqNSCLC, thereby improving efficacy and reducing undue toxicity.
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