Abstract 591P
Background
KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (nsqNSCLC). Tyrosine kinase inhibitors (TKIs)- sotorasib and adagrasib are approved for use in patients(pts) with KRASG12C variant. A novel TKIs- active in other KRAS variants are in development. Therefore all potentially targetable KRAS variants should be routinely tested in advanced NSCLC. The next generation sequencing (NGS) is recommended for simultaneous testing of potentially actionable biomarkers.
Methods
The study was performed as part of routine genetic diagnosis of pts with nsqNSCLC within a single institution between Jan.2019-May.2023. The material for the study consisted of tissue and cytologic samples containing no less than 20% of the tumor cells. The NGS method was used to assess the mutation status of the KRAS gene. Samples were sequenced using the FusionPlex CTL ArcherDx assay on a MiniSeq instrument (Illumina).
Results
In a group of 1468 real-world patients (pts) with advanced nsqNSCLC tested with NGS KRAS prevalence was 32,3% (474 pts). KRASG12C variant was observed in 229 pts representing 15,6% pts with nsqNSCLC and 48,3% of all KRAS mutant pts. In KRAS mutant group in cytological and tissue specimen the most common variants occurred accordingly in: Gly12Cys (50%, 48%), Gly12Asp (20%, 15%), Gly12Ala (9%, 8%), Gly12Val (14%, 15%), other variants less than 5% each (table). KRAS and other mutation coexisted in 7% (34 of 474) pts. The incidence of molecular KRAS variants diagnosed with NGS were comparable between the cytological and tissue specimen. Table: 591P
| Variant | All KRAS pts N=474 (100%) | Cytology N=88 (100%) | Tissue N=386 (100%) | |||
| N | % | N | % | N | % | |
| Gln61His | 20 | 4,22% | 2 | 2,27% | 18 | 4,7% |
| Gly12Ala | 40 | 8,44% | 8 | 9,09% | 32 | 8,3% |
| Gly12Asp | 75 | 15,82% | 18 | 20,45% | 57 | 14,8% |
| Gly12Cys | 229 | 48,31% | 44 | 50,00% | 185 | 47,9% |
| Gly12Val | 71 | 14,98% | 12 | 13,64% | 59 | 15,3% |
| Gly12Ser | 9 | 1,90% | 1 | 1,14% | 8 | 2,1% |
| Gln61Leu | 6 | 1,27% | 1 | 1,14% | 5 | 1,3% |
| exon2 | 8 | 1,69% | 1 | 1,14% | 7 | 1,8% |
| Gln61Lys | 7 | 1,48% | 1 | 1,14% | 6 | 1,6% |
| Gly12Phe | 4 | 0,84% | 0 | 0,00% | 4 | 1,0% |
| Gly12Arg | 2 | 0,42% | 0 | 0,00% | 2 | 0,5% |
| Lys117Asn | 1 | 0,21% | 0 | 0,00% | 1 | 0,3% |
| Gln61Arg | 2 | 0,42% | 0 | 0,00% | 2 | 0,5% |
Conclusions
The NGS is feasible for diagnosis of the KRAS mutations in real-world practice. The utility of both cytological and tissue testing is high for NGS profiling with comparable prevalence of the most frequent KRAS variants.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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