Abstract 134P
Background
Several reports showed that distinct KRAS alterations could display a different prognostic and therapeutic value in colorectal cancer (CRC). While the role of common KRAS (cKRAS) mutations has been investigated, there is little evidence on the impact of uncommon KRAS mutations (uKRAS).
Methods
Patients diagnosed with CRC between January 2015 and 2023 were retrospectively selected from Institutional pathology archives of the European Institute of Oncology and assessed r with a custom next-generation sequencing (NGS) panel or the Oncomine Comprehensive Assay v3. Detection of not previously described KRAS mutations was confirmed through direct sequencing. uKRAS alterations were defined as a variant with a frequency <1% according to cBioportal. Overall survival (OS), event free survival (EFS) and progression free survival (PFS) were estimated using the Kaplan–Meier method. Statistical analyses were performed using Jamovi.
Results
Thirty-four out of 2427 profiled patients (1.4%) presented uKRAS alterations. For 28 of those (82.5%) clinical informations were available. Median age was 62.5 years (41-80), with 16 male (57%) Most of patients (85%) had a localized disease at diagnosis stage I-III), and 4 had stage IV). The control group included 87 patients with cKRAS mutations and matched clinical characteristics. Patients with uKRAS mutations treated with radical surgery had lower EFS compared to cKRAS group [28 months (20-NR) vs 45 months (27-NR) HR 1.01 (0.53-1.93; p: 0.969)]. However, no difference in OS was observed. In the metastatic setting, a trend toward lower OS was observed between uKRAS and cKRAS patients [33 months (22-NR) vs 44 months (33-NR) (HR 2.27 (0.77-6.69; p: 0.137)], while no difference in PFS was reported.
Conclusions
Our study provides novel insights on the role of rare uKRAS mutations in CRC, which seems to be correlated with a more aggressive clinical behavior compared to cKRAS ones. Further investigations are required to confirm these hypothesis generating results.
Legal entity responsible for the study
European Institute of Oncology.
Funding
Has not received any funding.
Disclosure
D. Ciardiello: Other, Personal, Other, Travel Support: Merck KgA. N. Fusco: Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme (MSD), AstraZeneca, Daiichi Sankyo, GSK (GSK), Gilead, Novartis, Roche, Menarini, Lilly, Sysmex; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme (MSD), AstraZeneca, Menarini; Financial Interests, Personal and Institutional, Research Grant: Novartis, Sysmex, Veracyte. N. Fazio: Financial Interests, Personal, Other, Steering committee: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Merck, MSD, Novartis, Ipsen; Financial Interests, Institutional, Invited Speaker: Astellas, MSD, BeiGene, Nucana, Ipsen, Fibrogen; Financial Interests, Institutional, Research Grant: Ipsen, Novartis, Merck; Non-Financial Interests, Other, Steering committee: SPARC Europe; Non-Financial Interests, Member of Board of Directors: ENETS; Non-Financial Interests, Other, Member of the NET Faculty: ESMO; Non-Financial Interests, Other, Internal reviewer of NET guidelines: AIOM. E. Guerini Rocco: Financial Interests, Personal, Invited Speaker: AstraZeneca, Exact Sciences, GSK, Illumina, Novartis, Roche, Thermo Fisher Scientific; Financial Interests, Personal, Other, travel accommodation and expenses: AstraZeneca, Exact Sciences, GSK, Illumina, Novartis, Roche, Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Novartis, Roche; Financial Interests, Institutional, Funding: AstraZeneca, GSK; Financial Interests, Personal and Institutional, Research Grant: Thermo Fisher Scientific; Non-Financial Interests, Institutional, Product Samples: Thermo Fisher Scientific, Illumina, Agilent Technologies, Diatech Pharmacogenetics S.R.L., Biocartis. All other authors have declared no conflicts of interest.