Addressing Limited Treatment Options for Refractory CRC

Nicholas James Hornstein, MD, PhD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, and an author of the phase 2 INTERCEPT-TT study (NCT05343013), spoke with CancerNetwork® about recently published results in the Journal of Clinical Oncology.

TAS-102, an oral chemotherapy medication, demonstrated that, when administered following adjuvant chemotherapy, it induced circulating tumor DNA (ctDNA) clearance in patients with colorectal cancer (CRC) who have ctDNA-defined minimal residual disease. In the trial, 47% and 36% of patients who received TAS-102 had ctDNA clearance at 3 and 6 months, respectively, compared with 6.7% at 3 months (P = .0034) and 6.7% at 6 months (P = .025) in the synthetic control cohort.

According to Hornstein, the trial was necessary because there are limited treatment options for colorectal cancer after a patient has received treatment, then has the disease come back in a refractory setting; he referred to polychemotherapy as one of the few options.

ctDNA gives physicians an idea of when or if a patient’s tumor will return, and this trial was intended to identify if the disease could be stopped from making that return.

Transcript:

CRC is a disease that happens too often in the US, and although we are getting better at early detection, [such as performing] colonoscopies and doing screenings, the challenge is that even if we detect it at an early stage, meaning stage II or stage III, we cut it out, and we even give chemotherapy. Up to a third of patients end up having their disease come back in a refractory setting, and the challenge is past conventional polychemotherapy, we do not have [many] options, but we have developed tools now to monitor patients.

ctDNA has the ability for us to look for tiny pieces of DNA from the tumor that might still be present in the bloodstream. They give us this lead time of somewhere between 6 and 9 months of knowing, “Hey, the tumor is probably going to come back, but we don’t have an option for it.” TAS-102, in this setting, was an attempt to see, “Can we change the natural history of the disease if a patient has had all the treatment they’re supposed to get and they’re still ctDNA positive? Can we stop the disease from coming back?” That’s what this study was born out of.

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