586P - Minimal residual disease (MRD) detection using a tumour naïve circulating tumour DNA (ctDNA) assay in patients (pts) with resected colorectal cancer (CRC) in the phase III ASCOLT trial

Background

Although ctDNA is associated with MRD and recurrence in curatively treated CRC, implementation in clinical practice remains to be optimised. We evaluated the utility of a tumour naive ctDNA assay using serial prospectively collected plasma samples from the ASpirin for Dukes C and high risk Dukes B COLorecTal cancer trial (ASCOLT, NCT00565708), a large randomised phase III study of adjuvant aspirin.

Methods

Plasma samples were collected at baseline, 6 and 12 m in the Australian/ New Zealand cohort (n= 452). In a cohort of 118 pts matched by follow-up time (59 with recurrence [cases] and 59 non-recurrent [controls]), we used an ultra-sensitive ctDNA assay (SafeSEQ, Sysmex Inostics) for MRD detection. Cell pellets were analysed for mutations related to clonal haematopoiesis of indeterminate potential (CHIP). Results were correlated with recurrence and CEA.

Results

291 plasma samples (median 4.0 mL, median DNA 71.0 gen equiv/uL) were analysed (54/118 F; median age 68; 48 high risk stage II, 70 stage III; all had adjuvant chemotherapy; median follow-up 53.1 m). 59 pts recurred at median 12.4 m, of whom 32 had detectable ctDNA (sens 54%, Table). CEA sensitivity for detecting recurrence was 26%. Of the 27 pts with recurrence but no detectable ctDNA, 13 (48%) recurred >12 m after final sample collection. 8 pts without recorded recurrence had plasma mutations (CHIP analysis not available n = 3, all TP53). In multivariate analysis adjusting for known risk factors, ctDNA positivity was independently associated with recurrence (OR, 6.5; 95% CI, 2.2 – 18.9; p<0.001). Median time from 1st positive ctDNA to imaging detected recurrence was 7.9 m (range 0.2 – 40.2). ctDNA change over time and correlation with tumour sequencing will be presented. Table: 586P

Summary of ctDNA Data

*SafeSEQ 14 gene CRC MRD assay: AKT1, APC, BRAF, CTNNB1, ERBB3, FBXW7, KRAS, NRAS, PIK3CA, POLE, PPP2R1A, RNF43, SMAD4 and TP53

Conclusions

Tumour naïve, serial ctDNA detection within 1 year of adjuvant chemotherapy is independently associated with recurrence, noting limitations in sensitivity and specificity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Australasian Gastro-Intestinal Cancer Trials Group and Royal Australasian College of Physicians Foundation.

Disclosure

A. Starus: Non-Financial Interests, Institutional, Member, Anna Starus is an employee of Sysmex Inostics, Inc: Sysmex Inostics. F.S. Jones: Non-Financial Interests, Institutional, Member, Frederick Jones is an employee of Sysmex Inostics, Inc.: Sysmex Inostics. All other authors have declared no conflicts of interest.