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

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.

Detection of KRAS mutation using plasma samples in non-small-cell lung cancer: a systematic review and meta-analysis

“…Oncomine Lung cfDNA Assay (Thermo Fisher Scientific) showed sensitivity, specificity, and concordance rate of 61.54%, 93.83%, and 85.98%, respectively ( 30 ). Oncomine Lung Cell-Free Total Nucleic Acid Assay (Thermo Fisher Scientific) was used in three studies, and accuracy results varied greatly: sensitivity from 30.77% to 81.82%, specificity from 64% and 100%, and concordance rate from 52.63% to 94.44% ( 31 – 33 ). AmoyDx Essential NGS panel (Amoy Diagnostics) was used in a 28-patient cohort, and the sensitivity, specificity, and concordance rate were 66.67%, 96%, and 92.86%, respectively ( 34 ).…”

Liquid Biopsy Analysis as a Tool for TKI-Based Treatment in Non-Small Cell Lung Cancer

“…G12C cooccurred with other KRAS mutations in one case. This pilot study may suggest that in the assessment of the plasma, with KRAS G12C mutation as a druggable target, a real-time PCR assay through Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies [ 237 ].…”

Liquid Biopsy in Clinical Oncology

“…Количество мутантных копий гена, циркулирующих в крови, падает сразу же после начала терапии; в 60% случаев мутантная ДНК исчезает в течение 6-ти недель лечения [70]. На данный момент ЖБ уже достаточно хорошо адаптирована к использованию в клинической практике в отношении таких разновидностей опухолей, как рак легкого и рак толстой кишки [71][72][73][74][75].…”