ArticleCancer2025
Circulating tumor DNA dynamic variation predicts sotorasib efficacy in KRASp.G12C-mutated advanced non-small cell lung cancer.
Article in Cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Associations between early changes in circulating tumor DNA (ctDNA) and outcomes across randomized trials: Insights from the ctMoniTR project.The journal of liquid biopsy · 2026Article
- Exploring genomic analysis and methylome profiling in longitudinal series of p.G12C KRAS mutated NSCLC patients treated with sotorasib.The journal of liquid biopsy · 2026Article
- Systematic and precise interventions for KRAS-mutant cancers.Experimental hematology & oncology · 2026Review
- Circulating-tumour DNA (ctDNA) in NSCLC: mechanisms, evidence and the future of MRD detection.BMJ oncology · 2026Review
- Comprehensive Liquid Biopsy Approaches for the Clinical Management of Lung Cancer Using Multiple Biological Matrices.International journal of molecular sciences · 2025Review
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe objective of this study was to investigate the correlation between circulating tumor DNA (ctDNA) KRAS G12C-mutation dynamic variations and treatment outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving sotorasib therapy in a real-world setting.
methodsPeripheral blood samples were prospectively collected from 32 patients at baseline, at cycle 3, and then at each radiologic assessment during sotorasib treatment. Both tissue and plasma samples were analyzed by using ultra-deep, customized next-generation sequencing (NGS) assays. Plasma samples from 27 of 32 patients also were analyzed by digital polymerase chain reaction analysis, and ctDNA dynamic variations were correlated with radiologic responses and patients' clinical outcomes.
resultsA significant correlation between NGS and digital polymerase chain reaction-detected KRAS G12C variant allelic fractions (p < .001) was observed. Patients who achieved clearance of KRAS G12C-mutant ctDNA levels had a significant improvement in the objective response rate (80% vs. 8%; p < .001), median progression-free survival (7.9 vs. 2.8 months; p < .001), and median overall survival (16.8 vs. 6.4 months; p < .001) compared with those who did not achieve clearance. The clearance of ctDNA was the only prognostic factor significantly associated with both median progression-free survival (hazard ratio, 0.15; 95% confidence interval, 0.04-0.48) and median overall survival (hazard ratio, 0.09; 95% confidence interval, 0.02-0.45) in multivariable analysis. Moreover, a dynamic increase in the KRAS G12C median variant allele fraction anticipated radiologic disease progression in 70% of patients who were evaluable at the resistance time point.
conclusionsThis study demonstrated that early clearance of KRAS G12C-mutant ctDNA predicted the clinical benefit of sotorasib in patients with advanced NSCLC, suggesting that dynamic monitoring of ctDNA levels also may anticipate sotorasib resistance.
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