Jeanne Tie, MD, MBChB, on Colon Cancer: New Data on ctDNA Guiding Adjuvant Therapy

So the dynamic is a randomized trial looking at the utility of using CtDNA to guide adjuvant treatment in stage two colon cancer. The rationale behind the study is the fact that the role of adjuvant chemotherapy remains debatable in stage two colon cancer where surgery cured the majority of patients and to date, there has been very little evidence of survival benefit with the use of adjuvant chemotherapy. Our prior work have shown that detection of CtDNA after surgery is highly prognostic, where almost all patient recurred if left untreated. So this is a non-inferiority study that randomized patient to two-thirds receiving CtDNA guided management and one-third of standard management. So in the CtDNA guided group, patient with a positive result after surgery receive adjuvant chemotherapy and patient with a negative result were just observed. So the key findings from the study is that we have reduced the use of adjuvant chemotherapy by using CtDNA compared to standard management from 28% down to 15%, but we did not compromise recurrence-free survival. The updated results from dynamics showed that even at 5 years, the recurrence-free survival was 88.3% in the CtDNA guided group, and 87.2% with that of management of not using the blood test and the lower bound of the 95 confidence interval remains above the non-inferiority margin, again, confirming the non-inferiority of this approach. The overall survival between the two arms are similarly very favorable, ranging around 93%, which is very impressive. Intriguingly, we found that more than half the patient, substantial proportion of the death events in the study were not due to colorectal cancer recurrence resulting in a disease-specific survival, exceeding 97% across both arms. Another interesting finding is that we collected serial bloods on patient who have CtDNA positive and receive adjuvant chemotherapy. We found a very high clearance rate of 87.5% of CtDNA clearance following adjuvant chemotherapy, and patients who cleared a CtDNA had exceedingly good recurrence-free survival compared to patient who did not clear their CtDNA. So we also found that in untreated CtDNA negative T4 tumor, their overall survival is excellent at 19.6%. The implication for clinical practice is that using CtDNA to guide therapy compared to not having the blood test in stage two colon cancer can reduce the use of adjuvant chemotherapy without compromising patient's outcome and that CtDNA clearance rate is very high, supporting the benefit of adjuvant chemotherapy in this very high-risk population.