, 2025-05-01 13:41:00
Circulating tumor DNA (ctDNA) saw more success in guiding adjuvant therapy decisions, in a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2025.
The phase 2 trial screened for ctDNA in 174 patients with early-stage mismatch repair–deficient solid tumors — 16 types in all, the majority colorectal cancer — within 10 weeks of R0 resections and standard-of-care adjuvant therapy. Twenty-two were ctDNA positive.
Among the 22 ctDNA-positive patients, 13 were treated with pembrolizumab for 6 months. The remaining nine positive patients had experienced recurrence by the time they were screened and were not put on pembrolizumab.
Eleven of the 13 ctDNA-positive patients cleared their ctDNA by the finish of pembrolizumab, and the two others cleared it by 9 months.
Clearance was a good sign for most. Eight of the 13 (62%) were recurrence-free at a median follow up of 32.1 months, and overall survival (OS) among the group was 92% at 2 years.
Their OS results were similar to the 2-year survival rates (98%) among the 152 patients in the study who were ctDNA negative after surgery and observed, but 2-year recurrence free survival was a bit higher among patients who were ctDNA-negative, at 94%.
Meanwhile, among the nine subjects who were ctDNA positive after surgery and not treated with pembrolizumab, median time to recurrence was just 0.8 month and 2-year OS was 78%.
ctDNA-Guided Treatment May Help Prevent Relapse
In the end, “the study suggests ctDNA-guided treatment strategies may help prevent relapse in patients whose tumors would otherwise recur,” said lead investigator Yelena Janjigian, MD, a gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in Manhattan.
Using ctDNA to make the call on added treatment after surgery is the subject of much research in oncology. The idea is that patients with ctDNA after surgery are at higher risk for recurrence because they have microscopic cancer that needs to be treated, whereas patients who don’t have ctDNA in their blood are truly free of disease and can avoid the risks and costs of additional treatment.
Findings Lay Groundwork for Future Trials of ctDNA
The approach was supported by the DYNAMIC trial, a groundbreaking placebo-controlled study in stage 2 colorectal cancer that suggested that ctDNA negative patients don’t need added treatment after surgery. Numerous placebo-controlled trials are hoping to replicate the results in other tumor types.
Janjigian’s study was originally intended to be one of those placebo-controlled trials, but the placebo arm was closed early because patients and their doctors didn’t want to risk being randomized to a sham treatment, she said.
Despite the setback, Janjigian said her “study demonstrates that treating these patients with a ctDNA-guided adjuvant immunotherapy approach can effectively eliminate residual disease before macroscopic recurrence occurs.”
The findings “lay the groundwork for future trials to validate ctDNA as a predictive biomarker…ensuring that high-risk patients receive timely intervention while avoiding overtreatment,” she said.
The fact that some ctDNA-negative patients in the study still had tumor recurrences means that the largely in-house ctDNA testing used in the study had false negatives and that testing for ctDNA needs to improve, said trial discussant Maximilian Diehn, MD, PhD, a radiation oncologist at Stanford University in California.
“Hopefully, newer, ultrasensitive tests will really let us maximize the promise of” the approach, he said.
Diehn was also concerned that the trial wasn’t placebo-controlled. It’s unclear what a comparison would have looked like had there been a placebo group, he said.
Still, the approach holds promise, he said.
The study was funded by Merck, the maker of pembrolizumab, and Cycle for Survival. Janjigian is a consultant and speaker for Merck. Diehn isn’t involved with Merck but has other industry ties.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com
