582P - High accuracy of a blood-based multimodal ctDNA test to detect advanced neoplasms in a FIT-positive screening population

Background

Current colorectal cancer (CRC) screening assays decrease CRC-related incidence and mortality. However, effectiveness of screening programs is limited by the very low adherence of the population to screening recommendations. Development of less invasive, more accessible, and more convenient tests is an unmet clinical need.

Methods

A circulating tumor (ct)DNA blood-based assay that integrates genomics, epigenomics and fragmentomics was tested in blood samples from two cohorts: (1) consecutive FIT-positive individuals from the CRC Barcelona stool-based screening program; (2) patients diagnosed with CRC. Colonoscopy was performed in all individuals. Primary endpoint was to establish the accuracy of the assay to detect CRC and advanced adenomas (AA) compared to colonoscopy. A secondary exploratory endpoint analyzed the accuracy of a refined version of the assay (including protein and updating bioinformatic thresholding) to detect AA in a cohort of random FIT-positive individuals from the CRC screening program.

Results

A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection was high in all TNM stages (84% stage I, 94% stage II, 96% stage III, 100% stage IV). The test detected advanced neoplasms (AA or serrated lesion or CRC) with a sensitivity of 85% and a specificity of 90%. Sensitivity to detect AA was 23% when using a refined version of the test, with a specificity of 86%.

Conclusions

A blood-based multimodal ctDNA assay detected advanced neoplasms with high accuracy. This non-invasive, accessible, and convenient test is key to increase the population compliance to screening recommendations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Hospital del Mar, Barcelona.

Funding

Has not received any funding.

Disclosure

J. Vidal Barrull: Financial Interests, Personal, Invited Speaker: Merck, Pierre Fabre, Amgen; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. V.M. Raymond: Financial Interests, Personal, Full or part-time Employment: Guardant Healh. I. Faull: Financial Interests, Personal, Full or part-time Employment: Guardant Healh. B. Bellosillo Paricio: Non-Financial Interests, Personal, Funding: Thermo Fisher; Financial Interests, Personal, Funding: Roche Diagnostics, Roche Pharma, AstraZeneca; Financial Interests, Personal, Invited Speaker: Thermo Fisher, Qiagen, Merck; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca. C. Montagut Viladot: Non-Financial Interests, Institutional, Funding: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Guardant Health, Amgen, Lilly, Sanofi, Biocartis. All other authors have declared no conflicts of interest.