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. 2021 Nov 25;11(12):2196.
doi: 10.3390/diagnostics11122196.

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

Chiara Nicolazzo  1 , Alain Gelibter  2 , Irene Bottillo  3 , Francesca Belardinilli  4 , Simona Pisegna  2 , Gianluigi De Renzi  1 , Daniele Marinelli  2 , Paola Grammatico  3 , Enrico Cortesi  2 , Giuseppe Giannini  4 , Paola Gazzaniga  1
Affiliations

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

Chiara Nicolazzo et al. Diagnostics (Basel). .

Abstract

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies.

Keywords: KRAS G12C; circulating tumor DNA; clonal evolution; liquid biopsy; non-small-cell lung cancer.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

    1. Pennell N.A., Arcila M.E., Gandara D.R., West H. Biomarker Testing for Patients With Advanced Non-Small Cell Lung Cancer: Real-World Issues and Tough Choices. Am. Soc. Clin. Oncol. Educ. Book. 2019;39:531–542. doi: 10.1200/EDBK_237863. - DOI - PubMed
    1. Scheffler M., Ihle M.A., Hein R., Merkelbach-Bruse S., Scheel A.H., Siemanowski J., Brägelmann J., Kron A., Abedpour N., Ueckeroth F., et al. K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways. J. Thorac. Oncol. 2019;14:606–616. doi: 10.1016/j.jtho.2018.12.013. - DOI - PubMed
    1. Lanman B.A., Allen J.R., Allen J.G., Amegadzie A.K., Ashton K.S., Booker S.K., Chen J.J., Chen N., Frohn M.J., Goodman G., et al. Discovery of a Covalent Inhibitor of KRASG12C [AMG 510] for the Treatment of Solid Tumors. J. Med. Chem. 2020;63:52–65. doi: 10.1021/acs.jmedchem.9b01180. - DOI - PubMed
    1. Sidaway P. Sotorasib effective in KRAS-mutant NSCLC. Nat. Rev. Clin. Oncol. 2021;18:470. doi: 10.1038/s41571-021-00533-w. - DOI - PubMed
    1. Reck M., Spira A., Besse B., Wolf J., Skoulidis F., Borghaei H., Goto K., Park K., Griesinger F., Felip E., et al. CodeBreak 200: A phase III multicenter study of sotorasib [AMG 510], a KRAS[G12C] inhibitor, versus docetaxel in patients with previously treated advanced non-small cell lung cancer [NSCLC] harboring KRAS p.G12C mutation. Ann. Oncol. 2020;31((Suppl. 4)):S894–S895. doi: 10.1016/j.annonc.2020.08.1730. - DOI

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