Abstract 90P
Background
Colorectal cancer (CRC) is increasingly associated with molecular profiling. For several years, rat sarcoma virus (RAS) gene mutational status has been known as a negative predictive biomarker for anti-epidermal growth factor receptor antibodies treatment and is paramount in treatment choice. More recently, specific RAS mutations have been approached as therapeutic targets (such as Kirsten RAS (KRAS) G12Cys). However, there is a lack of analysis regarding clinical patterns, such as metastasis sites or survival prognosis. In our study, we aim to explore differences between specific RAS mutations regarding metastasis clinical patterns and prognosis.
Methods
Retrospective analysis of patients (pts) at 1 Portuguese tertiary centre with histologically confirmed metastatic CRC who were tested for KRAS/Neuroblastoma RAS (NRAS) mutations with Next-generation sequencing (NGS) between January 1st 2012 and December 31st 2021. Data cut-off was October 1st 2023. Data was obtained from pts' clinical files, collected in an anonymous registry and analyzed with SPSSv26.0.
Results
126 pts with RAS mutant mCRC were included; median age of 67 years (29-89), mostly male (79 pts); Thirty-seven pts reported active/former smoking habits, 33pts had prior/active alcohol consumption and 34 were overweight starting systemic therapy. Most primary tumours were left-sided (77 pts). Eighty-seven pts were metastatic ab initio. Most frequent metastatic sites were liver (87pts, of which 70 at diagnosis), lung (59 pts, 30 at diagnosis) and peritoneum (33 pts, 21 at diagnosis). KRAS G12Val mutation was the most frequent (32pts), followed by G12Asp (30 pts), G13Asp (21 pts) and G12Cys (8 pts). Mutations of KRAS codons 61, 146 and NRAS mutations were harbored by 6 pts each. Median overall survival was 23 months (95%CI 18.05 - 27.95). Patients harboring KRAS G12Val had poorer prognosis (p=.038), while pts harboring KRAS G12Asp mutation were more likely to have ab initio peritoneal disease (r=.3, p=.0001).
Conclusions
Increasing data suggests links between molecular profiling and pathological behaviour regarding CRC. In our population, only 8 pts harbored KRAS G12Cys mutation, which highlights the unmet need for novel RAS targeting drugs.
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.