Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study.

• DOI: 10.1200/jco.2024.42.3_suppl.9
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Pashtoon Murtaza ...; Vasily N. Aushev; Joe Ensor; Nathan Langer; Christopher Gene ...; Timothy Lewis Cannon; Lyudmyla Derby Berim; Trevor Feinstein; Axel Grothey; Joseph William Mc...; Sujith R. Kalmadi; Ahmed Zakari; Farshid Dayyani; Donald Gravenor; Janelle Marie Meyer; Saima Sharif; Adham A Jurdi; Minetta C. Liu; Alexey Aleshin; Scott Kopetz
• Keywords: Interim analysis; Circulating tumor DNA

9 Background: ctDNA-based post-surgical detection of molecular residual disease (MRD) is known to be predictive a high risk recurrence. Here, we report the first results BESPOKE CRC, multicenter, prospective, observational study evaluating ability tumor-informed ctDNA assay inform ACT treatment decisions in stage II/III CRC patients (pts). Methods: Of 1792 pts enrolled between 2020-07-02 and 2022-08-25, plasma samples from 350 with II-III were analyzed. was detected quantified using personalized, (Signatera, Natera, Inc.). Following curative resection, 232 received 118 underwent observation. Results: The cohort included 154 II 196 III pts; median follow-up 24.8 months. at post-op MRD time point (tp) available for 295 15.6% (46/295; II: 9/130=6.9%; III: 37/165=22.4%) positive (ctDNA+) tp (MRD+). MRD-positivity significantly associated inferior disease-free survival (DFS) stages combined (HR=20.8, 95% CI: 10.0-43.4, p<0.0001) stage-stratified subgroups (stage HR=25.7, CI 6.8-96.7; HR=18.1, 7.3-45.1). Within MRD+ group, receiving had longer DFS compared those observation group (median DFS: 18.7 vs 6.7 months; HR=3.9, 1.3-11.5, p=0.01). In contrast, no benefit observed MRD- (HR=1.1, 0.3-3.9, p=0.89). pts, 39.1% (18/46) clearance 12-weeks post-surgery tp. Pts who remained 24.2 13.8 HR=0.4, 0.1-1.0, p=0.045), however, worse than ctDNA- both 4- (HR=22.5, 6.8-75.0, p<0.0001). Notably, 44.4% (8/18) recurred; all 8 turned back ctDNA+ before radiological relapse. during surveillance 339 whom 8.3% (58/339) serially (HR=124.3, 29.8-518.7, Conclusions: highly prognostic recurrence an early representative subset cohort. Data expanded will presented meeting. also predictive: significant but not pts. Additionally, response adjuvant therapy status pt outcomes. Our highlight potential utility ctDNA-guided CRC. herein, as one prospective studies, further validated by ongoing ctDNA-directed randomized clinical trials. Clinical trial information: NCT04264702 .