319MO - Real-world monitoring of circulating tumor DNA reliably predicts cancer recurrence in patients with resected stages I-III colorectal cancer

Background

Despite earlier screening and advancements in diagnostic and treatment modalities, nearly 25-40% of patients with resected stage I-III colorectal cancer (CRC) recur. A novel approach to post-surgical risk stratification for molecular residual disease (MRD) detection and treatment monitoring is needed to improve patient outcomes.

Methods

In this retrospective analysis of a U.S-based multi-institutional study, data from commercial circulating tumor DNA (ctDNA) testing of approximately 12,000 stage I-III CRC patients were analyzed. Complete clinical data was available for 400 patients with 2,140 plasma samples collected between 06/2019-04/2022. A personalized, tumor-informed multiplex PCR-based next-generation sequencing assay (Signatera™) was used to quantify ctDNA prior to surgery, postoperatively (MRD-window; within 8 weeks of surgery, prior to therapy) and during surveillance.

Results

Of 12,000 patients, ctDNA during the MRD-window was tested in 5,684 patients with an overall ctDNA positivity rate of 22.1% (1,259/5,684) and higher positivity rates among stage III (29.5%, 805/2732) patients. In patients with available clinical data (N=400), ctDNA during the MRD-window was tested in 124 patients with a positivity rate of 21.8% (27/124). During the follow-up period (median 626 days; range: 0-3517 days), 63.0% (17/27) of MRD-positive patients relapsed compared to 9.3% (9/97) of MRD-negative patients. Notably, of these 9 relapsed MRD-negative patients, 7 became ctDNA-positive on serial testing beyond 8 weeks. ctDNA positivity during the MRD-window, anytime post-surgery and during surveillance was significantly associated with shorter recurrence-free survival (HR=12.2, 95%CI: 5.3−27.8, p<0.0001), (HR=16.7, 95%CI: 7.4−37.4, p<0.0001), and (HR=25.4, 95%CI: 12.6−51.3, p<0.0001), respectively.

Conclusions

In this study utilizing real-world data from patients with early-stage CRC, postsurgical ctDNA detection at any time point was prognostic of relapse. Postsurgical ctDNA testing in early-stage CRC patients may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Natera, Inc.

Funding

Has not received any funding.

Disclosure

S.A. Cohen: Financial Interests, Personal, Advisory Board: Boston Biomedical, Polaris; Financial Interests, Personal, Speaker’s Bureau: Natera, Inc. P.M. Kasi: Financial Interests, Personal, Advisory Board, Consultancy/Advisory Board: Foundation Medicine, Natera Oncology, AstraZeneca, Merck MSD, Tempus, Bayer, Lilly, Delicath Systems, QED Therapeutics, Servier, Taiho Oncology, Exact Sciences, Eisai; Financial Interests, Institutional, Advisory Board, Consultancy/Advisory Board: Taiho, Ipsen; Financial Interests, Institutional, Funding, Investigator initiated trial cooperative group PI trial support and funding.: Tersera; Financial Interests, Institutional, Funding, Investigator initiated trial trial support and funding.: Boston Scientific. V.N. Aushev: Financial Interests, Personal and Institutional, Stocks/Shares: Natera, Inc. D.L. Hanna: Financial Interests, Personal, Advisory Board: Natera, Inc. G.P. Botta: Financial Interests, Personal, Advisory Board: Natera, Inc.; Financial Interests, Personal, Invited Speaker: Natera; Financial Interests, Personal, Funding: Carsgen. G. Laliotis: Financial Interests, Personal and Institutional, Stocks/Shares: Natera, Inc. S. Sharma: Financial Interests, Personal and Institutional, Stocks/Shares: Natera, Inc. S.R. Chandana: Financial Interests, Personal, Invited Speaker: Natera, Inc. S. Chakrabarti: Financial Interests, Personal, Invited Speaker, Speaker bureau: Natera Inc; Financial Interests, Personal, Other, Advisory role: QED THerapeutics. A. Kasi: Financial Interests, Personal, Other, Honoraria: OncLive; Financial Interests, Institutional, Funding: Tesaro, Halozyme, Astellas Pharma, Rafael Pharmaceuticals, Geistlich Pharma, Cardiff Oncology, FibroGen, Bavarian Nordic, Novocure; Financial Interests, Personal, Other, travel, accomodations: Halozyme, Rafael Pharmaceuticals. F. Dayyani: Financial Interests, Personal, Advisory Board: AstraZeneca, Natera, Inc., Exelixis, Genetech; Financial Interests, Personal, Other: Deciphera, Eisai, Exelixis, Ipsen, Natera, Inc., Sirtex; Financial Interests, Personal, Other, Natera, Inc.: Servier; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, Taiho, Exelixis, Merck, Natera, Inc., Ipsen; Financial Interests, Personal, Research Grant, Natera, Inc.: Trishula. M. Malla: Financial Interests, Personal and Institutional, Research Grant, (Grant # 5U54GM104942-05): National Institute of General Medical Sciences-NIH; Financial Interests, Personal, Advisory Role, Natera, Inc.: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Natera, Inc.. A. Jurdi: Financial Interests, Personal and Institutional, Stocks/Shares: Natera, Inc.. A. Aleshin: Financial Interests, Personal and Institutional, Stocks/Shares: Natera, Inc.. 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, Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GlaxoSmithKline, Jazz, Xilis, Abbvie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Other, Research: Inivata; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis. All other authors have declared no conflicts of interest.