TAS-102 Achieves ctDNA Clearance, Improves DFS in Colorectal Cancer

In the phase 2 INTERCEPT-TT trial (NCT05343013), TAS-102 demonstrated improved levels of circulating tumor DNA (ctDNA) clearance vs a synthetic control cohort in patients with colorectal cancer.

CancerNetwork® spoke with Nicholas James Hornstein, MD, PhD, about the most significant efficacy findings from this trial. He highlighted the enhanced ctDNA clearance with TAS-102, which was 47% and 36% at 3 and 6 months, respectively; in the synthetic control cohort, the rate was lower, with only 2 patients achieving ctDNA clearance at 3 months (P = .0034) and sustaining it to 6 months (P = .025).

He also discussed the disease-free survival (DFS) and progression-free survival (PFS) results from the trial. Of the 9 patients receiving TAS-102 who had radiographic recurrence, the median DFS was 9.4 months vs 5.75 months among 28 patients in the synthetic control cohort who had radiographic recurrence (P = .03).

Hornstein, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, and an author of the study, finished by saying that better treatments are needed.

Transcript:

The primary findings were that at 6 and at 9 months, a large number of patients—more than would be expected by chance—had their ctDNA cleared by giving them TAS-102. Compared with the synthetic cohort, where about 2 of 30 patients randomly had their ctDNA cleared, we had around 37% to 47% of patients have their ctDNA cleared. Seven out of 15…. That’s considerably higher than 2 of 30. It seems like TAS-102 did a good job of helping to clear ctDNA.

DFS and PFS are important things to keep in mind because, at the end of the day, we care if the cancer comes back, and we care if it’s curable. One of the challenges with TAS-102 is it seems like it was able to tamp down on the ctDNA positivity, but it [couldn’t] eradicate it. Many of these patients did go on to have radiographic recurrence. The DFS was longer than it would have been expected otherwise, without TAS-102, but the question is, “What more can we do for these patients?” This is, to me, a proof of principle. We can intervene and we can affect ctDNA positivity, but frankly, I like TAS-102 as an agent, but we need better drugs than we have right now to clear ctDNA and cure patients, because that’s the goal.

References

Pellatt AJ, Bent A, Hornstein N, et al. Phase II trial of TAS-102 in colorectal cancer patients with circulating tumor DNA-defined minimal residual disease after adjuvant therapy: INTERCEPT-TT. JCO Precis Oncol. 2025;9:e2500142. doi:10.1200/PO-25-00142