Liquid biopsy may save colon cancer patients from chemo

CHICAGO — Patients with early colon cancer who have detected tumor DNA circulating in the blood may need more aggressive treatment, but people who have a negative liquid biopsy appear to be safe to avoid chemotherapy — without increased risk of recurrence, the researchers suggested here.

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

In his presentation of the results of the DYNAMIC trial (Circulating Tumor DNA Analysis Informing Adjuvant Chemotherapy in Stage II Colon Cancer) at the annual meeting of the American Society of Clinical Oncology (ASCO) MeetingTie said 2-year disease-free survival was 93.5% in patients who were negative for circulating tumor DNA and excluded from chemotherapy and 92.4% in those who received unguided standard management. by a liquid biopsy, meeting the criteria of non-inferiority.

At 3 years, the 92% disease-free survival rate in DNA-negative patients for the circulating tumor who had not received chemotherapy was similar to that of patients who had been managed according to conventional criteria, a- she reported at a press conference. The results were also published in the New England Journal of Medicine.

“The results of the DYNAMIC study are very encouraging, as previous data suggest that patients with a positive circulating tumor DNA score after surgery have a very high risk of recurrence if no other treatment is given. Our results show that ‘with adjuvant therapy, circulating tumor DNA-positive patients derive significant benefit from chemotherapy, such as an oxaliplatin-based regimen,’ Tie said.

In the trial, 455 patients diagnosed with stage II colon cancer were enrolled in the study and underwent surgery to remove the cancer. Four to 7 weeks after surgery, patients were randomized to undergo management based on liquid biopsy results, while a second group of patients were treated with standard treatment – patient-guided management. clinician based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor has perforated the bowel wall, and other factors.

For DNA-guided management of circulating tumors, a positive result after surgery led to chemotherapy treatment with oxaliplatin or fluoropyrimidine. Patients with negative results did not receive chemotherapy after surgery.

About 53% of the patients were men; the median age of trial participants was 64 years and approximately 27% of trial patients were 70 years of age or older. Almost everyone in the study was in the Eastern Cooperative Oncology Group’s 0-1 performance status. The median follow-up was 37 months, Tie reported.

The study also included some cases of stage II rectal cancer who had not received chemoradiotherapy before surgery; these cancers were generally treated like colon cancers.

“For the most part, the patients who tested negative on the test used in the study had no circulating tumor DNA signal,” Tie said. MedPage Today. She said there were a few cases that had a very weak and inconclusive signal, which were also called negative. “No test is perfect,” she said.

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

Commenting on the study, Julie Gralow, MD, ASCO’s chief medical officer and executive vice president, said MedPage today: “It’s really an interesting trial. It’s part of a concept now in settings where we get great results – few relapses and few deaths – of treatment de-escalation. That is, we can can we step back in treatment Can we find subgroups of patients who may not need all of the aggressive therapy?

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

Gralow added: “Now we should be looking at the subset that really needs more therapy – even the escalation of therapy beyond standard therapy, and the group where we can back off and avoid chemotherapy and all these treatment-related toxicities, and still get the same results.” She also pointed to the “big difference in relapse rate” between people who were positive and negative for circulating tumor DNA.

Tie reported that the 3-year disease-free survival was 86.4% in patients DNA positive for circulating tumor who received adjuvant chemotherapy and 92.5% in patients DNA negative for circulating tumor. circulating tumor who have not received chemotherapy.

“What we need to do is in this group that has the presence of circulating tumor DNA, we need to look at strategies to choose other treatments, not just chemotherapy, such as genomics-based targeted agents. of cancer so that we can bring this group to the excellent survival level of the group whose circulating tumor DNA is negative,” Gralow said.

“We should seek to optimize therapy so that some patients are intensified and others have their treatment de-initiated, and we will find exactly the right treatment for each tumor in each patient,” she added.