50P - KRAS mutation, the molecular landscape of lung adenocarcinoma in the Portuguese population

Background

Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are detected in over 1/3 of non–small-cell lung cancer (NSCLC) subtype, representing the most prevalent genomic driver event. Mostly located in codons 12 and 13, the most frequent is the p.Gly12Cys (c.34G.T) (G12C), representing about 20-25% of KRAS drive mutations in NSCLs, but remains scarce. The impact of them on prognosis is currently subject to debate, as is their impact on the response to chemotherapy and EGFR tyrosine kinase inhibitors. Our goal was to stratify our population, reporting the KRAS mutation frequency in a series of Portuguese NSCLC cases, in order to observe the incidence and impact of change of practice.

Methods

Retrospective study included NSCLC samples submitted for KRAS testing at one Portuguese center in Lisbon, between 1/1/2027 and 31/12/2021. Data cut-off was 1/9/2022. KRAS mutational status was evaluated from tumor biopsy using a new generation sequencing technique on DNA obtained to detect the most common mutations of the KRAS gene. The Oncomine™ Focus Assay panel was used in the IPATIMUP laboratory. Data was obtained from pts' clinical files and analyzed with SPSSv26.0.

Results

101 pts with NSCLC were included in our analysis, median age of 66 years (44-87), 70% male, with good performance status (70% ECOG PS 0-1). Concerning tobacco consumption, 80% were active smokers. Regarding tumor characteristics, all cases were adenocarcinomas, with 46% N1 at diagnosis and 56% of pts M1 ad initium. 10% were relapses. PDL1 status was positive in 40% of pts, and unknown in 2%. Mutation KRAS G12C was the status most frequent, identified in 36,6% of the population including c.34G>T p.Gly12Cys (36 pts) and c.35G>A p.Gly12Cys (1 pt). Followed by c.35G>T p.Gly12Val in 21,7% (22pts), c.35G>A p.Gly12Asp in 13,8% (14pts) and c.35G>C p.Gly12Ala in 6,93% (7). 1,98% (2pts) had 2 KRAS different mutation observed c.34G>T p.Gly12Cys+c.37G>A p.Gly13Ser and c.35G>T p.Gly12Val+c427G>A p.Glu143Lys where the combinations.

Conclusions

Our representative population presented a slight raise in the frequency of the G12C mutation, showing that approximately 36% of Portuguese pts with NSCLC harbor the G12C variant, thus potentially responsive to the new anti-KRAS agents.

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.