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.
Resources from the same session
570P - First-line osimertinib for patients with advanced NSCLC harboring EGFR mutations: A real-world study
Presenter: Wenxiang Ji
Session: Poster Display
Resources:
Abstract
571P - Dacomitinib in treatment-naïve EGFR-mutant NSCLC patients with multiple brain metastases: Initial efficacy and safety data from a phase II study
Presenter: Yongfeng Yu
Session: Poster Display
Resources:
Abstract
572P - Multivariable five-year survival prediction model for prognosing patients with EGFR-mutated NSCLC treated with EGFR-TKIs
Presenter: Qi-An Wang
Session: Poster Display
Resources:
Abstract
573P - LUMINATE-103: Real-world treatment patterns and outcomes of patients (pts) with epidermal growth factor receptor mutant (EGFR MU), non-squamous (NSQ) locally advanced/metastatic non-small cell lung cancer (a/mNSCLC): Pooled analysis of large US electronic health record (EHR) datasets
Presenter: Byoung Chul Cho
Session: Poster Display
Resources:
Abstract
574P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC harboring uncommon EGFR mutations
Presenter: Lin Wu
Session: Poster Display
Resources:
Abstract
575P - Efficacy and safety of dacomitinib in treatment-naïve patients with advanced NSCLC and brain metastasis: A multicenter cohort study
Presenter: Puyuan Xing
Session: Poster Display
Resources:
Abstract
576P - Clonality of both EGFR and co-occurring TP53 mutations affect the treatment efficacy of the third-generation EGFR-TKIs in advanced-stage EGFR-mutant non-small cell lung cancer
Presenter: Wen Feng Fang
Session: Poster Display
Resources:
Abstract
577P - A study of the efficacy and safety of amivantamab in EGFR exon 20 insertion (E20I) mutations in NSCLC
Presenter: Daeho Choi
Session: Poster Display
Resources:
Abstract
578P - Tyrosine kinase inhibitor treatment of elderly patients with epidermal growth factor receptor mutated advanced non-small cell lung cancer: A multi-institute retrospective study
Presenter: Ling-Jen Hung
Session: Poster Display
Resources:
Abstract
579P - Real-world study of dacomitinib as first-line treatment for patients with EGFR-mutant non-small cell lung cancer
Presenter: Ji Eun Shin
Session: Poster Display
Resources:
Abstract