587P - Short lead time and high rates of concomitant radiographic recurrences for ctDNA-based minimal residual disease assays colorectal cancer (CRC) during surveillance: Results from the MD Anderson INTERCEPT program

Background

Although observational cohorts have shown that detection of circulating tumor DNA (ctDNA)-defined minimal residual disease (MRD) following curative intent therapy has a lead time of over 9 months (m) prior to radiographic recurrence, real world data (RWD) where results are returned to patients and providers are lacking. This is especially important since these studies have not incorporated rigorous clinical evaluation for concomitant recurrence.

Methods

In the INTERECEPT program, pts with stages II-IV CRC treated with curative intent at MD Anderson Cancer Center between 1/1/2022 and 31/12/2022 were evaluated with a tumor-informed MRD assay (Signatera, Natera) with an overarching goal to generate RWD and to integrate MRD-based testing into CRC pt care. Surveillance evaluations were per established guidelines; ctDNA was recommended post-operatively and q3m with each surveillance visit. Pts and providers were informed of the results; subsequent clinical decisions and courses were tracked.

Results

Of 847 pts (median 57y, [21-93], 55% were male; stage% I-III/IV were 69/31; colon/rectum% were 61/39. 20.5% (n=174) of pts had a positive ctDNA assay during surveillance, prompting imaging tests in 99% of cases (CT scan in 157 pts, PET/CT in 13 pts, MRI in 3 pts). These radiological investigations demonstrated definitive disease in 48% of cases, indeterminate findings in 11% and no evidence of disease in 41% of cases. Of those with indeterminate findings, 17/19 had a recurrence confirmation with a 2^nd imaging modality. The median time to radiologic recurrence after a positive ctDNA result was less than 2 months. For those patients without radiologic recurrence identify concurrently with ctDNA+, the median time to recurrence was 3 months.

Conclusions

CRC pts on surveillance who are ctDNA+ are likely to have radiographic recurrence identify upon further investigation. The potential clinical benefit of this earlier radiographic identification of recurrent disease remains to be determined. True MRD pts (ctDNA+ but radiographically -ve) have a lead time providing a potential opportunity for therapeutic intervention.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

MD Anderson Cancer Center.

Funding

MD Anderson Cancer Center.

Disclosure

N.A. Dasari: Financial Interests, Personal, Advisory Board: HutchMed, AAA, Personalis, Illumina, Ipsen; Financial Interests, Institutional, Trial Chair: HutchMed, Eisai, Guardant Health, Natera, Xencor, Taiho; Financial Interests, Institutional, Coordinating PI: Enterome. E.S. Kopetz: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, Merck, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca, Bayer, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GSK, Jazz, Xilis, AbbVie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Other, Research: Inivata, Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis; Financial Interests, Personal, Other, Consultant: Genomic Health, Frontier Medicines, Replimune, Taiho Pharmaceutical, Cardiff Oncology, Ono Pharmaceutical, Bristol Myers Squibb, Medarex, Amgen, Tempus, Foundation Medicine, Harbinger Oncology, Takeda, CureTeq, Zentalis, Black Stone Therapeutics, NeoGenomics Laboratories, Accademia Nazionale Di Medicina; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis; Financial Interests, Personal, Ownership Interest: Frontier Medicines. All other authors have declared no conflicts of interest.