Abstract 79P
Background
Kirsten rat sarcoma viral oncogene mutation (KRASm) is detected in approximately 25% of non-small cell lung cancer (NSCLC) adenocarcinoma patients (pts). As Next-generation sequencing (NGS) has been increasingly employed, diverse KRASm subtypes (subt) with different prognoses, incidences of co-mutations and characteristics have been described.
Methods
We performed NGS to all stages NSCLC pts from 2019 to 2021. Tissue genotyping was performed through Illumina Focus, a 52 genes targeted NGS panel that simultaneously analyzes DNA and RNA alterations. In addition, a single test for rearrangement assessment was done in necessary cases. Programmed death ligand-1 (PD-L1) expression was tested by SP263 antibody. We analyzed the clinical and pathological characteristics of KRASm pts.
Results
A total of 62 from 213 pts had KRASm. Median age was 67 years [49-92], 79% were male, 87.1% adenocarcinomas, and only 8.1% non-smokers. In 19.4% of pts, NGS was sufficient for molecular characterization, but in 75.8% a single molecular test had to be added. KRASm subt in our cohort were: G12C (33.9%), G12V (25.8%), G12D (21%) and Q61H (6.5%). G12V was more frequent in non-smokers (60%). Coexistent mutations were determined in 24.2% of pts and the most frequent was PIK3CA. PD-L1 >50% was present in 19.4% of pts. No association was detected between KRAS subt and PD-L1 expression level or co-mutations. Significant differences were observed between KRAS subt and clinical stage. Early-stages represented the 24.19% of KRASm pts and 40% of them had G12D. G12C and G12V KRASm were associated with a higher incidence of metastatic disease (p 0.004). Differences in median overall survival were observed over all subtypes (G12V 8.24 months (m), Q61H 10.28 m, G12C 12.45 m, G12D Not reached), although they were not statistically significant (p 0.5). Co-mutation presence and high PD-L1 expression confered worse prognoses (p 0.4 and p 0.08 respectively).
Conclusions
Our results suggest the importance of knowing the KRAS status and its subtype in NSCLC. This is necessary in metastatic patients but also in the early stages, taking into account the relationship observed between the subtype and the risk of metastasis. PD-L1 status could be a prognostic factor in KRASm patients, but more investigations are required.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Climent Vicente: Financial Interests, Personal, Other, travel accommodation: Roche, Rovi; Financial Interests, Personal, Member, travel accommodation: Lilly. N. Lopez Zurita: Financial Interests, Personal, Speaker’s Bureau: Esteve; Financial Interests, Personal, Other, travel and accommodation: Rovi, Novartis. J. Giner Joaquin: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS. S. Soriano: Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin, MSD; Financial Interests, Personal, Other, travel and accommodation: Pierre Fabre, Rovi, Roche. P. Ribera Fernandez: Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Other, travel and accommodation: Lilly, Merck, Amgen, Sanofi. M. Rodriguez: Financial Interests, Personal, Other, travel and accommodation: Roche, Ipsen, Amgen, BMS; Financial Interests, Personal, Speaker’s Bureau: Rovi. P. Andreu Cobo: Financial Interests, Personal, Other, travel and accommodation: Rovi. M. Busquets Godall: Financial Interests, Personal, Other, travel and accommodation: Rovi, Lilly, Bristol, Leopharma. M. Fragio Gil: Financial Interests, Personal, Other, travel and accommodation: Rovi, Leopharma, Bristol, Lilly. O. Cano i Cano: Financial Interests, Personal, Other, travel and accommodation: Vifor. A. Carrasco Navas: Financial Interests, Personal, Other, travel and accommodation: Lilly. M.S. Sierra Boada: Financial Interests, Personal, Other, travel and accommodation: Rovi, Lilly. L. Vila Martinez: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck, Roche, BMS, Pfizer.