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

ESMO Open

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R. Serna-Blasco¹  E. Sánchez-Herrero¹  S. Sanz-Moreno¹  A. Rodriguez-Festa¹  E. García-Veros¹  M. Casarrubios¹  B. Sierra-Rodero¹  R. Laza-Briviesca¹  A. Cruz-Bermúdez¹  X. Mielgo-Rubio³  A. Sánchez-Hernández⁴  E.A. Uribelarrea⁵  V. Calvo⁶  A. Romero¹  M. Provencio¹ 

[1] Molecular Oncology Laboratory, Biomedical Sciences Research Institute Puerta de Hierro-Majadahonda University Hospital;Atrys Health;Medical Oncology Department, Hospital Universitario Fundación Alcorcón;Medical Oncology Department, Hospital Provincial Centre de Castelló;Medical Oncology Department, Hospital Universitario de Cruces;Medical Oncology Department, Hospital Universitario Puerta de Hierro

关键词: KRAS;    G12C;    NSCLC;    EGFR;   

DOI  :  10.1016/j.esmoop.2021.100279

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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.

【 授权许可】

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