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KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor
- Source :
- Biblos-e Archivo. Repositorio Institucional de la UAM, instname, ESMO Open
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. Materials and methods: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. Results: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. Conclusions: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature<br />This work was supported by CLARIFY project (https://www.clarify2020.eu/). ES-H was supported by the Consejería de Ciencia, Universidades e Innovación of the Comunidad de Madrid (Doctorados Industriales of the Comunidad de Madrid) [grant number IND2019/BMD-17258]. EG-V was supported by AECC (Asociación española Contra el Cáncer) grant ‘Programa de Prácticas de Laboratorio de curso académico AECC 2020’ (no grant number).
- Subjects :
- Cancer Research
Lung Neoplasms
Medicina
medicine.drug_class
EGFR
NSCLC
medicine.disease_cause
Tyrosine-kinase inhibitor
Proto-Oncogene Proteins p21(ras)
Carcinoma, Non-Small-Cell Lung
G12C
KRAS
Humans
Medicine
Digital polymerase chain reaction
Lung cancer
Protein Kinase Inhibitors
neoplasms
Original Research
business.industry
Resistance mutation
medicine.disease
respiratory tract diseases
ErbB Receptors
First line treatment
Oncology
Mutation
Mutation (genetic algorithm)
Cancer research
business
Tyrosine kinase
Subjects
Details
- ISSN :
- 20597029
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- ESMO Open
- Accession number :
- edsair.doi.dedup.....f94a2a9cb28c5b9162e637d8517f5f9d