500P - Molecular features in liquid biopsy of early (EO) and late-onset colorectal cancer (LO)

Background

Incidence of colorectal cancer (CRC) in patients (pts) younger than 50 years (y) or Early-Onset Colorectal Cancer (EO), is rising worldwide. This trend has prompted an earlier initiation age of screening in some countries, and also focused the research on molecular biology of this entity.

Methods

We prospectively enrolled pts with previously untreated metastatic CRC. Blood sample was submitted for comprehensive ctDNA analysis with Guardant360 at baseline (BL) and at tumor progression (P). We described the total number of genetic alterations, Variant Allele Fraction (VAF) and main variants found in two age-of-onset groups: EO (<50 y) and LO (≥50 y).

Results

Of 155 recruited pts, 14 (9%) were EO. In EO group, 14.3% of pts were diagnosed at localised stages (I-III), in contrast with 20.6% in LO. Primary tumors were right sided in 28.6% of EO, and 24.3% of LO. Regarding the number of genetic alterations, we observed a median of 4 per patient at BL and 3 at P in EO, and 5 (BL) and 4 (P) for LO. Median and range of VAF (based on maximum VAF for each patient) was 0.139% (0.013-0.836%) at BL and 0.317% (0.064-0.476%) at P, in EO and 0.149% (0.0005-0.896%) at BL and 0.09% (0.001-0.846%) at P in LO. The genomic landscape showed some differences in prevalent alterations (Table). Among genes with highest VAF in both groups were: APC, TP53, KRAS, SMAD4, PIK3CA, and BRAF. However, in LO we found also NRAS, PTEN, ARID1A and ATM; and in EO, instead, FBXW7, ERBB2, BRCA2 and EGFR. Table. Table: 500P

Genomic alterations with different prevalence (fraction of total alterations) in age based groups

Conclusions

EO pts seem to have some distinct molecular features that can be captured in comprehensive liquid biopsy. The clinical value needs to be further explored.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

UGC Intercentros de Oncología Médica. Hospitales Universitarios Regional y Virgen de la Victoria. IBIMA.

Funding

Guardant Health.

Disclosure

J. Alcaide-Garcia: Financial Interests, Personal, Invited Speaker: Amgen; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Roche; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Amgen; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Servier; Non-Financial Interests, Personal, Other, Travel and accommodation expenses: Merck; Non-Financial Interests, Personal, Other, Travel and accommodation expenses : Sanofi. M. Benavides: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Institutional, Product Samples: Guardant Health. M. Alvarez: Financial Interests, Personal, Advisory Board: Bristol; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Nanostring. I. Sevilla: Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pharmamar; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: AAA. V. Navarro Perez: Financial Interests, Personal, Invited Speaker: Bristol; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis. M. Kushnir: Financial Interests, Personal, Full or part-time Employment: Guardant Health. I. Faull: Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.