ctDNA identifies colon cancer patients who can skip chemotherapy

‘Liquid biopsy’ reveals spread of ctDNA after stage II surgery Colon Cancer It helps identify patients who are likely to benefit from adjuvant chemotherapy, and also identifies those who are unlikely to benefit from being allowed to skip this treatment.

Results from the Phase II DYNAMIC trial.

Commented first author Jane Tai, MD, of the Walter and Elisa Hall Institute for Medical Research at The Peter McCallum Cancer Center, University of Melbourne, Australia.

She added that the overall proportion of patients who were alive and free of cancer at 3 years after ctDNA-directed therapy was 92% – the same percentage in patients randomized to standard management.

She said the chance of cancer-free survival was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and ctDNA-negative patients who did not. Conversely, the risk of recurrence is greater than 80% without treatment in patients with ctDNA.

Tai announced the results here at the 2022 American Society of Clinical Oncology annual meeting, which was Published simultaneously In the New England Journal of Medicine.

The study supports a ctDNA-directed approach to treatment in this group of patients, Tay said, noting that this approach addresses what has been a clinical dilemma: Surgery can treat more than 80% of stage 2 patients, but the benefits of postoperative chemotherapy have been Less clear – fewer than 1 in 20 patients would benefit, but the ability to predict which patients would benefit was lacking.

Julie Gralow, MD, chief medical officer of ASCO and executive vice president, commented that the findings changed practice.

“I see this study as an important kind of new concept in cancers, where we often have very good survival and outcomes…and now we’re starting to look for ways we can reduce treatment escalation in the subgroup we are in,” Gralow said at a press briefing where the study was highlighted. We know that they will do well while continuing with the more intense treatment, or even escalating treatment, in the group that we know will not work well with our conventional treatments.”

“I think the results will help us guide our choice of who benefits from chemotherapy and who can avoid it – and all the toxicities from it – in stage 2 colon cancer,” she added.

They can also identify patients who may need more than standard treatment. This is a group where “we may need to think outside the box and do more besides just thinking about adjuvant chemotherapy,” she said Medscape Medical News In a pre-conference interview. “Maybe this is a group where we should think about adjuvant immunotherapy, for example, or therapy directed toward the abnormal growth factor growth factor (EGFR), or other things that we’ve shown [to have benefit] in the metastatic environment”.

Study details

For the DYNAMIC trial, Tie and colleagues enrolled 455 patients with resected stage II colon cancer at multiple centers between August 2015 and August 2019. Of these, 302 patients were randomized to receive ctDNA-guided chemotherapy and 153 received standard administration based on conventional criteria, Including the stage of the pathological tumor, the number of lymph nodes evaluated, whether the tumor has perforated the intestinal wall, and other factors.

The Security SeqS A tumor-informed personal ctDNA assay was used to detect ctDNA in the experimental group. Patients with a positive ctDNA result at 4 or 7 weeks after surgery received oxaliplatin or fluoropyrimidine-based chemotherapy. Those who were negative for ctDNA were observed during follow-up.

Fewer patients overall in the ctDNA-directed group, compared to the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).

The 2-year recurrence-free survival (RFS) in the ctDNA-directed treatment group was inferior to that in the standard management group (93.5% vs. 92.4%). The three-year RFS was 86.4% in ctDNA-negative patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in the low-risk clinical subgroup.

Cathy Eng, an expert at ASCO, praised the results, saying in a press release that “thanks to the results of this study, we may now be able to use them to better identify a stage II colon cancer patient who would benefit from postoperative treatment with chemotherapy and which one could be avoided from further treatment, without compromising relapse-survival.”

Inge is the David H. Johnson Chair in Surgery and Oncology, Co-Leader of the Digestive Cancer Research Program, Co-Director of Gastrointestinal Oncology, and Professor of Medicine in Hematology and Oncology at Vanderbilt University, Nashville, Tennessee.

Next steps

The authors note that a randomized trial is being considered in which patients present and negative for ctDNA are selected to treatment versus no treatment. This may provide more specific evidence of a treatment’s effect, or no effect, in each patient subgroup, according to the press release.

The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, the US National Institutes of Health, the Marcus Foundation, the Virginia and DK Ludwig Cancer Research Fund, the Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, the John Templeton Foundation and the Eastern Health Research Foundation . Tie reported receiving honors from Inivata and Servier, and served as a consultant or advisor to AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, Pierre Fabre.

ASCO 2022. Abstract LBA100. It was introduced on June 4, 2022.

In Engel J Med. Published online June 4, 2022. Full text

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, and writes for Medscape, MDedge, and other affiliated websites. She currently covers oncology, but has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on Twitter: Tweet embed.

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