Liquid Biopsy May Save Colon Cancer Patients From Chemo

CHICAGO – Early colon cancer patients who have circulating tumor DNA detected in blood may need more aggressive treatment, but people who have a negative liquid biopsy appear to be safe in avoiding chemotherapy – without increased risk of recurrence, researchers suggested here.

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

In her presentation of the results of the Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage II Colon Cancer (DYNAMIC) trial at the annual meeting of the American Society of Clinical Oncology (ASCO) meeting, Tie said that the 2-year disease-free survival was 93.5% in those patients who were negative for circulating tumor DNA and were excluded from chemotherapy and 92.4% among those who got standard managment not guided by liquid biopsy, meeting criteria for non-inferiority.

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

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

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

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

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

The study also included some cases of stage II rectal cancer that had not received chemoradiation prior to surgery; these cancers were generally treated like colon cancers.

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

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

In commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told MedPage Today: “This is really an interesting trial. It is part of a concept now in settings where we are getting really excellent outcomes – few relapses and few deaths – of de-escalation of treatment. That is, can we back off in treatment? Can we find subsets of patients that may not need all of the aggressive therapy?

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

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

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

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

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