Evaluation of KRAS G12C Mutation in Non–Small-Cell Lung Cancer Demonstrates Genetic Profile Differences Between Initial Diagnosis and Progressive Disease

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Precision medicine has advanced the treatment of patients with non–small-cell lung cancer (NSCLC) by using biomarkers or genetic alterations to guide treatment selection.1 Biopsy is used to obtain tumor samples, which are then tested to detect these biomarkers or genetic mutations.1 However, one problem frequently associated with biopsy is inadequate tissue sampling, especially in NSCLC, as tumor tissue can be difficult to access in the lung.1 This often means that invasive procedures need to be performed, resulting in inadequate sampling to perform the necessary comprehensive molecular profiling to direct treatment.1 Liquid biopsy, or analysis of tumor-derived material obtained from blood or other body fluids, may provide a solution to this challenge.1 In NSCLC, circulating tumor DNA or tumor cells are the most widely studied liquid biopsy samples.1 These 2 sample types can be used in multiple ways: as screening tools to detect NSCLC at earlier stages, to guide targeted therapy, to monitor treatment response, and to determine genetic changes that may result in treatment resistance.1 Liquid biopsy can also capture spatial and temporal heterogeneity that is missed with tissue biopsy.1 NSCLC will eventually progress despite treatment, and the tumor genetic profile may be different than found at disease diagnosis.1 Liquid biopsy at this stage can be an effective and safe way to obtain a sample to further analyze the disease and to guide further treatment.

At the European Society for Medical Oncology Congress 2021, Gianluigi De Renzi, PhD, presented the results of a study of 2 blood-based KRAS G12C genotyping tests at progressive disease in 38 patients with NSCLC. All patients had previous first-line immunotherapy treatment with primary tumor tissue mutational analysis being performed using next-generation sequencing. Blood samples were obtained from the patients and centrifuged. The plasma was removed, centrifuged, and screened for KRAS G12C mutation with real-time polymerase chain reaction and then further sequenced. In 24% of the plasma samples, KRAS G12C mutation was found, although the mutation was not detected in previous diagnostic tumor samples. All patients who tested positive for KRAS G12C mutation at baseline tissue sampling had negative circulating DNA at progressive disease.

The findings from this study demonstrated that KRAS G12C mutation can be lost or acquired at progressive disease stage, which may influence treatment success or failure.


De Renzi G, Nicolazzo C, Pisegna S, et al. Liquid biopsy to track KRAS G12C mutation at progressive disease in patients with advanced non-small cell lung cancer (NSCLC). Ann Oncol. 2021;32(suppl_5):S983.


  1. Guibert N, Pradines A, Favre G, Mazieres J. Current and future applications of liquid biopsy in nonsmall cell lung cancer from early to advanced stages. Eur Respir Rev. 2020;29:190052.

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