medwireNews: A large US study has shown the feasibility of circulating tumor (ct)DNA analysis to detect KRAS G12C mutations in patients with solid tumors.
The researchers explain that the novel KRAS G12C inhibitors sotorasib and adagrasib have shown promising efficacy in recent studies, “boosting the need for robust genotyping for this marker in oncology practice.”
They continue: “Moreover, upon disease progression, given the demonstrated role and emergence of KRASG12C mutations, both as primary and acquired resistance mechanisms, real-time genomic insights with ctDNA analysis can [help] to inform further line of therapy.”
The team therefore reviewed the ctDNA results from 80,911 treatment-naïve or previously treated patients with metastatic solid tumors who underwent Guardant360 (Guardant Health, Redwood City, California, USA) testing between July 2014 and June 2019.
KRAS G12C mutations were detected in 3.7% of patients, most commonly in those with nonsquamous non-small-cell lung cancer (NSCLC) and NSCLC not otherwise subtyped, at rates of 7.5% and 6.9%, respectively, followed by cancer of unknown primary, colorectal cancer, and squamous NSCLC, at 4.1%, 3.5%, and 2.0%.
Focusing on the 129 patients with KRAS G12C-positive cancer who had both ctDNA and tissue biopsy results available, the researchers found a high concordance between the modalities for cases where the liquid and tissue biopsies were performed within 6 months (time synchronous), but not for those where the tests were done more than 6 months apart (time asynchronous).
The positive predictive values for the synchronous and asynchronous groups were 98% and 77%, respectively, report David Hong (The University of Texas MD Anderson Cancer Center, Houston, USA) and co-investigators in JCO Precision Oncology.
They say that these findings suggest that either liquid or tissue biopsy “can be used for up-front profiling,” while “the greater discordance seen in time asynchronous cases reinforced the importance of evolving genomic landscapes under treatment pressure” and the value of ctDNA analysis in this setting.
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