ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non-Small Cell Lung Cancer Patients.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Plasma ctDNA kinetics as a predictor of systemic therapy response for advanced non-small cell lung cancer: a systematic review and meta-analysis.The oncologist · 2025Pooled it
- Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer.Cancer discovery · 2024Trial
- 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
- Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.Frontiers in genetics · 2026Review
- Circulating-tumour DNA (ctDNA) in NSCLC: mechanisms, evidence and the future of MRD detection.BMJ oncology · 2026Review
- Review
- KRAS G12C Inhibition in Solid Tumors: Biological Breakthroughs, Clinical Evidence, and Open Challenges.Cancers · 2025Review
- Molecular determinants of sotorasib clinical efficacy in KRASNature medicine · 2025Article
- Integration of Liquid Biopsy for Optimal Management of Non-small Cell Lung Cancer.Tuberculosis and respiratory diseases · 2025Article
- Article
- The growing field of liquid biopsy and its Snowball effect on reshaping cancer management.The journal of liquid biopsy · 2025Review
- Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials.Nature reviews. Clinical oncology · 2025Review
- Advances in the treatment of KRASCancer · 2025Review
- Early monitoring of plasma KRAS G12C with digital PCR predicts antitumor response to immunotherapy or sotorasib in advanced NSCLC: A brief report.The journal of liquid biopsy · 2024Article
- Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Targeting therapy-persistent residual disease.Nature cancer · 2024Review
- Targeting KRAS in cancer.Nature medicine · 2024Review
- Clinical application of liquid biopsy genomic profiling in NSCLC: Asian perspectives.The journal of liquid biopsy · 2024Review
- The sooner, the better: early clearance of plasma circulating tumor DNA in patients with advancedTranslational lung cancer research · 2024Article
- SOS1 inhibition enhances the efficacy of and delays resistance to G12C inhibitors in lung adenocarcinoma.bioRxiv : the preprint server for biology · 2023Article
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15 authors at 7 institutions in 1 country.
Funding
Abstract
purposeNon-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here, we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS G12C-mutant lung cancer. EXPERIMENTAL
designWe performed serial droplet digital PCR (ddPCR) and plasma NGS on 60 KRAS G12C-mutant patients with lung cancer that participated in cohort A of the KRYSTAL-1 clinical trial. We analyzed the change in ctDNA at 2 specific intervals: Between cycles 1 and 2 and at cycle 4. Changes in ctDNA were compared with clinical and radiographic response.
resultsWe found that, in general, a maximal response in KRAS G12C ctDNA levels could be observed during the initial approximately 3-week treatment period, well before the first scan at approximately 6 weeks. 35 patients (89.7%) exhibited a decrease in KRAS G12C cfDNA >90% and 33 patients (84.6%) achieved complete clearance by cycle 2. Patients with complete ctDNA clearance at cycle 2 showed an improved objective response rate (ORR) compared with patients with incomplete ctDNA clearance (60.6% vs. 33.3%). Furthermore, complete ctDNA clearance at cycle 4 was associated with an improved overall survival (14.7 vs. 5.4 months) and progression-free survival (HR, 0.3).
conclusionsThese results support using early plasma response of KRAS G12C assessed at approximately 3 weeks to anticipate the likelihood of a favorable objective clinical response.
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