81MO - Clinical experience of a personalized and tumour-informed circulating tumour DNA assay for minimal residual disease detection in oligometastatic colorectal cancer patients

Background

For patients with oligometastatic colorectal cancer (CRC) treated with definitive management with curative intent, >50% still recur post-resection. Circulating tumor DNA (ctDNA) testing can be used to assess minimal residual disease (MRD) in these patients and predict the risk of recurrence. Prospective evaluation of this methodology in clinical practice has been limited to date and the use of adjuvant chemotherapy (ACT) after metastasectomy is based on data extrapolated from earlier stage CRC.

Methods

A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA for MRD assessment. We present results from an ongoing early adopter program of ctDNA testing in patients with oligometastatic CRC (largely isolated to the liver) treated with surgery, radiation, or other definitive metastasis therapy. ACT was given at the discretion of the treating physician.

Results

ctDNA levels were analyzed in 93 oligometastatic CRC patients, post-resection/ablation (range 3 – 150 days, median 52 days). In the pre-surgical setting, ctDNA was detected in 100% (9/9) of the patients. Post-treatment MRD was detected in 49% (26/53) of patients, with an average of 454.15 mean tumor molecules/mL (range 0.11 - 13,274 MTM/mL, median 5.61 MTM/mL). MRD rates in patients post-oligometastatic therapy were found to be higher than in historical non-metastatic patients who had the same assay post-surgery (49% vs 18%). Longitudinal case studies describing the ctDNA clearance effects of ACT on MRD rates in the post-metastasectomy setting will be presented.

Conclusions

This is the largest set of clinical experience data analyzing ctDNA in oligometastatic CRC patients and shows definitive evidence that a highly sensitive MRD assay can detect residual disease after curative intent procedures. An average MRD rate of 49% is consistent with published relapse rates of ∼50% post-oligometastatic resection, suggesting this assay accurately measures residual disease and may be prognostic for relapse, as well as potentially predictive for who might benefit from post-metastasectomy ACT.

Clinical trial identification

NA

Editorial acknowledgement

Editorial support was provided by Meenaksh Malhotra, Ph.D. from Natera, Inc.

Legal entity responsible for the study

The authors.

Funding

Natera, Inc.

Disclosure

S.A. Cohen: Advisory/Consultancy: Natera, Inc.; Research grant/Funding (self): Boston Medical Polaris; Research grant/Funding (self): Isofol. N. Hook, S. Krinshpun, L. Westbrook, K. Loranger, J. Wallace, S. Sharma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. A. Aleshin: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Advisory/Consultancy: Mission Bio; Advisory/Consultancy: Notable Labs. P. Billings: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Advisory/Consultancy: Mission Bio.