Circulating tumor DNA for detection of molecular residual disease (MRD) in patients (pts) with stage II/III colorectal cancer (CRC): Final analysis of the BESPOKE CRC sub-cohort.

• DOI: 10.1200/jco.2025.43.4_suppl.15
• Publication Date: 2025-01-27T14:31:24Z
• Authors: Purvi K. Shah; Vasily N. Aushev; Joe Ensor; Stephanie A Sanchez; Christopher Gene ...; Timothy Lewis Cannon; Lyudmyla Derby Berim; Trevor Feinstein; Axel Grothey; Joseph William Mc...; Sujith R. Kalmadi; Ahmed Zakari; Farshid Dayyani; Don Gravenor; Minetta C. Liu; Adham A Jurdi; Alexey Aleshin; Janelle Marie Meyer; Saima Sharif; Scott Kopetz
• Keywords: Bespoke; Minimal Residual Disease

15 Background: BESPOKE CRC, a multicenter, prospective, observational study investigated the clinical utility of ctDNA for detecting MRD-based early recurrence in pts with surgically resected CRC. The primary endpoint was to assess impact testing on treatment decisions and asymptomatic rates. secondary MRD clearance rate, survival MRD-negative pts, overall survival, patient-reported outcomes. Methods: Complete laboratory data were available 1001 stages II–III Longitudinal performed prospectively using clinically validated, personalized, tumor-informed 16-plex mPCR-NGS assay (Signatera, Natera, Inc.). Plasma time points (n=8,536) collected during (2-12 weeks postoperatively) surveillance (post-adjuvant chemotherapy [ACT] completion/12 postoperatively observed) windows. We evaluated correlation between status disease-free (DFS) as part exploratory analysis. Results: Following curative resection, 62.4% (625/1001) received ACT: 25.9% (115/443) stage II, 91.3% (510/558) III.Among results window median follow-up 23.15 (range: 2.89-33.45) months, ctDNA-positivity observed 8.1% (34/420) II 24.9% (126/505) III pts. A significant association positivity inferior DFS (HR=10.4; p<0.0001), (HR=10.1, p<0.0001) 18/24 month estimates II-III combined were: (MRD-negative: 93.0%/91.7%; MRD-positive: 44.4%/41.4%). Analysis separately (N=368) vs. ACT-treated (N=597). During surveillance, observation cohort, 6.8% (22/323) 33.3% (15/45) tested ctDNA-positive correlating significantly worse (stage II: HR=34.9; p<0.0001, III: HR=34.1; p=0.0008). Likewise, ACT 10.9% (12/110) 21.1% (103/487) turned had HR=131.4; HR=54.6; p<0.0001). endpoints will be presented. Conclusions: highly prognostic within windows subset enrolled CRC study. Our highlight potential value ctDNA-based detection treatment-decision making, findings relevant reported conference presentation. Clinical trial information: NCT04264702 .