Abstract 4567: Circulating tumor DNA-based molecular residual disease guides treatment in metastatic colorectal cancer patients with no evidence of disease: An open-label, prospective, interventional phase II study

Abstract Patients with metastatic colorectal cancer (mCRC) can achieve no evidence of disease (NED) after curative treatment. However, the survival benefit of adjuvant chemotherapy (ACT) for these patients remains uncertain. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection has shown to help predict recurrence risk in CRC. Recent retrospective studies have indicated that ACT offers no clinical benefit in surgically resected mCRC with negative ctDNA. In this study, we conducted a prospective, interventiaonal clinical trial (NCT05635630) to evaluate the efficacy of ctDNA-guided ACT in patients with mCRC who achieved NED. Eligible mCRC patients who achieved NED after curative treatment were enrolled. Surgical tissues or puncture tissues were sequenced by whole-exon sequencing, and up to 50 highly ranked patient-specific variants were selected for the personalized panel design. Post curative treatment blood samples was sequenced by the personalized panel to determine the MRD status. Patients with positive MRD post curative treatment were offered investigator-determined ACT, while those with negative MRD were under surveillance. During surveillance, blood samples were collected every 3 months and patients whose MRD turned positive would receive intensive image surveillance every 2 months. A total of 104 eligible patients were included in the current analysis, among them 7 patients did not receive assigned treatment strictly adhered to the study protocol and were excluded from the per protocol set (PPS). In the PPS, as date cutoff of October 2024, the median follow-up was 14 months with 58 patients (58/97, 59.8%) who experienced recurrence. MRD was detected in 53 patients (54.6%, 53/97) post curative treatment. The median recurrence-free survival (RFS) was 8.5 months and not reached for patients with positive or negative MRD post curative treatment, respectively (HR: 4.28, 95% CI: 2.36-7.77; P<0.001). Six patients with negative MRD received ACT and had non-superior RFS than those who did not receive ACT (HR: 1.60, 95% CI: 0.46-5.58; P = 0.46). During surveillance, the median RFS was 6.1 months, 11.8 months, 16.8 months and not reached in patients with persistently positive ctDNA, converted positive ctDNA, converted negative ctDNA, and persistently negative ctDNA, respectively (log-rank P for trend <0.0001). All recurrent patients had at least one positive ctDNA detection before imaging confirmed recurrence, and the median lead time interval of ctDNA positivity to radiographic recurrence was 7.8 months (range, 0-20.2 months). Our results demonstrated the feasibility of using ctDNA to guide ACT in mCRC patients with NED. Future randomized clinical trials are needed to further demonstrate the utility of ctDNA-guided ACT in mCRC patients with NED. The follow-up is still on-going. Citation Format: Yaqi Li, Chengcheng Li, Peng Cui, Xiang Hu, Fangqi Liu, Wenhua Li, Guoqiang Wang, Kunli Zhao, Qi Pan, Jing Wang, Bing Li, Shangli Cai, Junjie Peng. Circulating tumor DNA-based molecular residual disease guides treatment in metastatic colorectal cancer patients with no evidence of disease: An open-label, prospective, interventional phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4567.