In a phase 2/3 study, among patients with detectable ctDNA after surgery for stage II colon cancer, the use of adjuvant chemotherapy did not increase the rate of ctDNA clearance.

These results were presented by Van K. Morris, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on Saturday, January 20, 2024, in San Francisco, California.

In this phase 2/3 trial, 635 patients with resected stage II colon cancer without traditional high-risk features and were deemed suitable for active surveillance were randomized on a 1-to-1 basis to receive either the standard-of-care observation (n = 318), or ctDNA assay-directed therapy (n = 317). Following surgery, blood samples were analyzed for ctDNA with the Guardant LUNAR assay for colon cancer-relevant mutations and colon cancer-specific methylation profiling. Patients in the ctDNA therapy arm with ctDNA detected received 6 months of adjuvant chemotherapy (either CAPOX or FOLFOX). The primary end point was clearance of ctDNA at the 6-month timepoint.

Among the first 16 patients with detectable ctDNA at baseline, clearance of ctDNA at 6 months was seen in 3 of 7 patients in the control arm and 1 of 9 patients in the ctDNA-directed therapy arm after chemotherapy (P = .98). The phase 2 end point was not met. Further enrollment has been halted.

According to Dr Morris and coauthors, “Further trials evaluating ctDNA as an integral biomarker for minimal residual disease determination must account for assay specificity in this [patient] population.” Dr Morris added, “Continued enhancements to ctDNA assay characteristics and performance coupled with the unmet clinical needs of patients keep future ctDNA trials highly relevant for the foreseeable future.”

ASCO expert Cathy Eng, MD, echoed Dr Morris, stating, “While the investigatos’ pre-planned interim analysis was unable to determine any improvement in ctDNA clearance, the role of ctDNA must continue to be explored.”

Source:

Morris VK, Yothers G, Kopetz S, et al. hase II results of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA) phase II/III study. Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract 5

New Study Adds to Ambiguity of Role of Post-Operative ctDNA to Guide Treatment in Patients With Low-Risk, Stage IIA Colon Cancer. ASCO. January 16, 2024. https://old-prod.asco.org/about-asco/press-center/news-releases/new-study-adds-ambiguity-role-post-operative-ctdna-guide