Abstract 50P
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.
Resources from the same session
13P - Universal prospects of cryopreserved umbilical cord blood CD34+ progenitor cell-derived NK cells: Clinical and preclinical evaluation of non-engineered and genetically engineered candidates
Presenter: Anna-Maria Georgoudaki
Session: Cocktail & Poster Display session
Resources:
Abstract
14P - Lentivirally overexpressed c-Myc promoter binding protein (MBP-1) localizes in the cytoplasm of human cutaneous melanoma cell lines increasing cell proliferation and glycolysis rate
Presenter: Miriam Hippner-Kunicka
Session: Cocktail & Poster Display session
Resources:
Abstract
15P - Enhancement Platform for immune Cells (EPiC): invIOs’s innovative cell-therapy platform for creating personalized cancer treatments
Presenter: Mario Kuttke
Session: Cocktail & Poster Display session
Resources:
Abstract
16P - Melatonin modulates energy metabolism and kinases signaling in ovarian cancer cells
Presenter: Luiz Gustavo Chuffa
Session: Cocktail & Poster Display session
Resources:
Abstract
17P - New therapeutic target in triple-negative breast cancer for enhancing PARP inhibitor efficacy and stimulating the anti-tumour immune response
Presenter: Marina Rodriguez-Candela Mateos
Session: Cocktail & Poster Display session
Resources:
Abstract
18P - PARP1 trapping and hyperactivation by the decoy agonist OX425 induces DNA repair abrogation and a robust anti-tumor immune response
Presenter: Vlada Zakharova
Session: Cocktail & Poster Display session
Resources:
Abstract
20P - Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Presenter: Pranshu Sahgal
Session: Cocktail & Poster Display session
Resources:
Abstract
21P - Cross-resistance between platinum-based chemotherapy (PlCh) and PARP inhibitors (PARPi) in castration-resistant prostate cancer (CRPC)
Presenter: Peter Slootbeek
Session: Cocktail & Poster Display session
Resources:
Abstract
22P - Emerging role of histone acetyltransferase CBP in breast cancer cells undergoing DNA damage
Presenter: Wafaa Ramadan
Session: Cocktail & Poster Display session
Resources:
Abstract
23P - Synthetic lethality by targeting RHEB in ARID1A-mutated luminal breast cancer
Presenter: Deniz Gulfem Ozturk
Session: Cocktail & Poster Display session
Resources:
Abstract