and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.