Ben Ho Park, MD, PhD

The invited discussant of the DYNAMIC study was Ben Ho Park, MD, PhD, who said the study “has really moved the needle for circulating tumor DNA [ctDNA] analysis and guiding therapy.” Dr. Park is Director of the Vanderbilt-Ingram Cancer Center, Nashville.

Speaking more broadly about the use of ctDNA testing in cancer, Dr. Park said: “A lot of work has been done in the past decade to prove that ctDNA is a valid clinical marker…. The challenge then becomes, what do we do with that? Can we take that knowledge and effect change that’s going to be a positive outcome, whether it’s de-escalating therapies or escalating therapies for our patients with cancer?” he asked.

Dr. Park continued: “What’s heartening is how we are now starting to push ctDNA into clinical utility,” though challenges in employing these tests still “plague” clinicians. Although ctDNA is commercially available, it is mostly, if not exclusively, used in the metastatic setting and is generally viewed as a tool for identifying actionable mutations. Other technical challenges include issues related to sensitivity, specificity, and positive and negative predictive values.

Moving Toward Clinical Utility

The stage II colon cancer setting “has been fraught with challenges and difficulties in identifying who will benefit from and who should receive adjuvant chemotherapy,” Dr. Park said. This is the issue tackled by the DYNAMIC trial, whose investigators he commended for conducting the initial clinical validation in this space. “This ‘dynamic’ trial takes this to the next step, toward clinical utility.”

The study not only confirmed its overall goal of noninferiority, but, in fact, it demonstrated “huge clinical utility” by halving the number of patients who received adjuvant chemotherapy, supporting the current trend for de-escalation of therapy, he noted.

However, ctDNA can still miss some patients who will relapse. This weakness might be overcome by combining the test with clinical risk markers, “in which case the negative predictive value becomes acceptable,” suggested Dr. Park. “I think the study also provides a safety net for testing novel therapies for ctDNA-positive patients.” 

DISCLOSURE: Dr. Park reported financial relationships with Loxo, Celcuity, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, and Lilly.