At the Gastrointestinal Cancers Symposium in San Francisco, two separate studies presented mixed results regarding the use of liquid biopsy for guiding colon cancer treatment.
In the first study, adjuvant chemotherapy guided by postoperative circulating tumor (ct) DNA did not lead to higher rates of DNA clearance compared with patients who did not receive chemotherapy. However, ctDNA showed promise in identifying patients with molecular residual disease (MRD) who might benefit from chemotherapy. Notably, patients who had sustained ctDNA clearance exhibited superior disease-free survival (DFS) compared to those with transient clearance, which was still better than no clearance.
The study, which included seven patients with detectable ctDNA, found that three of them subsequently had clearance during observation, compared to one out of eleven patients assigned to chemotherapy. The trial was terminated early for futility after an interim analysis.
In the second study, patients who were ctDNA-positive after surgery but achieved ctDNA clearance 6 months post-chemotherapy had a 24-month DFS of 90%. ctDNA status was a better predictor of DFS than clinicopathologic factors, according to Hiroki Yukami, MD, of Osaka Medical and Pharmaceutical University in Japan.
Despite these mixed results, ctDNA remains a powerful prognostic factor for recurrence in colorectal cancer. Aparna Parikh, MD, of Mass General Cancer Center in Boston, emphasized the importance of adapting to improving technologies and harmonizing the timing of testing. She agreed with the need to store samples for future comparison of tests.
The COBRA study, a phase II/III trial, evaluated ctDNA as a predictive marker for adjuvant chemotherapy in stage II colon cancer. The GALAXY trial, which included 2,998 patients, showed that ctDNA positivity in the MRD window is predictive of inferior DFS. The study highlighted the significance of ctDNA status during surveillance and the potential of ctDNA-guided adjuvant strategies, which will be further established by ongoing randomized interventional trials.