THE EFFECTIVENESS of circulating tumour DNA (ctDNA), also known as liquid biopsy, as a prognostic tool for guiding and monitoring cancer treatment remains uncertain. The NRG-GI005 (COBRA) Phase II/III study, the first of its kind, aimed to assess ctDNA clearance as a primary endpoint using adjuvant chemotherapy in patients with Stage II colon cancer. Unfortunately, the trial was discontinued during the planned Phase II analysis, as chemotherapy did not enhance ctDNA clearance compared to close observation alone. The research findings were to be presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.
The study involved 635 patients with resected Stage II colon cancer lacking traditional high-risk features. Participants were randomly assigned to two arms: Arm A (close observation without chemotherapy) and Arm B (ctDNA assay-directed therapy). Arm B patients without ctDNA detection continued observation, while those with detected ctDNA received 6 months of adjuvant (CAPOX or FOLFOX) chemotherapy. The primary endpoint was ctDNA clearance after 6 months.
Analysing the first 16 patients with detected ctDNA, the study planned to stop if P>0.35, indicating futility. Among these patients, ctDNA clearance after 6 months occurred in 43% of Arm A, and 11% of Arm B (P=0.98). The study was terminated following the Phase II endpoint non-fulfilment.
Lead author Van K. Morris, University of Texas MD Anderson Cancer Center, Houston, USA, expressed disappointment in the trial’s outcome, but emphasised the rapidly evolving real-world applications of liquid biopsy in GI cancers. Despite this setback, improvements in ctDNA assay characteristics and performance, along with the ongoing clinical needs of patients, underscore the ongoing relevance of future ctDNA trials. The study plans to continue monitoring participants for survival and recurrence outcomes.