Liquid biopsy can save colon cancer patients from chemotherapy

CHICAGO – Early colon cancer patients who have been found circulating tumor DNA in their blood may need more aggressive treatment, but people who have a negative liquid biopsy seem safe to avoid chemotherapy – without an increased risk of recurrence, the researchers suggested. .

About 28% of patients diagnosed with stage II colon cancer who were treated with standard therapy received adjuvant chemotherapy, but only 15% of patients who underwent liquid biopsy were treated with chemotherapy, said Jeanne Tie, MD, MBChB, of Walter and Eliza. Hall Institute of Medicine / Peter MacCallum Cancer Center in Melbourne, Australia.

In her presentation of circulating tumor DNA analysis for adjuvant chemotherapy for stage II colon cancer (DYNAMIC) at the annual meeting of the American Society of Clinical Oncology (ASCO), Tie stated that the two-year disease-free survival period was 93.5% in those patients who were negative for circulating tumor DNA and were excluded from chemotherapy, and 92.4% of those who received standard treatment that did not undergo liquid biopsy meeting the criteria for non-inferiority.

At 3 years, disease-free survival was 92% in patients with circulating DNA-negative tumors who did not receive chemotherapy, similar to patients treated according to conventional criteria, she told a news conference. The results were also published in New England Journal of Medicine.

“The results of the DYNAMIC study are very encouraging because previous data suggest that patients with a positive circulating tumor DNA score after surgery have a very high risk of recurrence if no further treatment is given. Our findings show that circulating tumor DNA-positive patients they benefit greatly from chemotherapy, such as an oxaliplatin-based regimen, ”said Tie.

The study included 455 patients with a diagnosis of stage II colon cancer who underwent surgery to remove the cancer. Four to seven weeks after surgery, patients were randomized to treatment based on liquid biopsy findings, while a second group of patients were treated with standard therapy – clinician-led treatment based on conventional criteria, including tumor stage, lymph node count, tumor perforation, and other factors.

For management-driven circulating tumor DNA treatment, a positive postoperative result resulted in oxaliplatin or fluoropyrimidine chemotherapy. Patients with negative results did not receive chemotherapy after surgery.

About 53% of patients were male; the median age of the study participants was 64 years, and about 27% of the patients in the study were 70 years of age or older. Almost everyone in the study had an Eastern Cooperative Oncology group of 0-1. The median follow-up was 37 months, Tie said.

The study also included some cases of stage II rectal cancer that had not undergone chemoradiation before surgery; these cancers were generally treated as colon cancer.

“Most patients who tested negative for the test used in the study had no signal of circulating tumor DNA,” Tie said. MedPage today. She said there were several cases that had a very low and inconclusive signal that were also called negative. “No test is perfect,” she said.

The test is not currently commercially available, but Tie suggested it would be available within a few months. At the time, she said she would incorporate the test into her clinical and treatment algorithm.

Commenting on the study, Julie Gralow, MD, chief physician and executive vice president of ASCO, said MedPage Today: “This is a really interesting study. It is part of a concept that is now in an environment where we get really great results – few relapses and few deaths – deescalation of treatment. Does that mean we can give up treatment? Can we find subgroups of patients who may not need all aggressive therapy?

“In stage II colorectal cancer, we probably know we’re giving too much chemotherapy,” she said. “We use conventional, classic pathological features to decide which patients with stage II colon cancer will receive chemotherapy after surgery. This study looked at whether we could use circulating tumor DNA – a liquid biopsy – to see if there was evidence of micrometastatic residual cancer. between 4 and 7 weeks after surgery and use them to decide whether or not patients should receive chemotherapy. “

Gralow added: “Now we should look at the subgroup that really needs further therapy – even escalating therapy beyond standard therapy, and the group where we can back down and avoid chemotherapy and all those treatment-related toxicities, and still get the same results. She also pointed to a “large difference in the number of relapses” between positive and negative circulating tumor DNA.

Tie reported that 3-year recurrence-free survival was 86.4% in circulating DNA-positive patients receiving adjuvant chemotherapy and 92.5% in circulating DNA-negative patients who did not receive chemotherapy.

“What we need to do is that in the group with the presence of circulating tumor DNA, we need to look at strategies to select other treatments, not just chemotherapy, such as cancer genomics-targeted targets, so that we can bring this group to an excellent level. survival of the group that circulates tumor DNA negative, “said Gralow.

“We should try to optimize the therapy so that in some patients it is escalated and in others the treatment is de-escalated, and we will find exactly the right treatment for each tumor in each patient,” she added.