Managing Dose Reductions With TAS-102 Therapy in Colorectal Cancer

During a conversation with CancerNetwork®, Nicholas James Hornstein, MD, PhD, discussed results from the phase 2 INTERCEPT-TT trial (NCT05343013) that evaluated TAS-102 against synthetic control in patients with colorectal cancer.

The trial met its primary end point, showing an improvement in circulating tumor DNA (ctDNA) clearance with TAS-102, and also showed an improvement in disease-free survival with the agent compared with the synthetic control cohort.

Regarding safety, no new safety concerns with the agent were noted, and the most common toxicities were hematological, gastrointestinal, and constitutional. Neutropenia occurred in 93.3% of patients, being grade 3 or higher in 73.3%, and grade 4 in 1 patient; lymphopenia occurred in 40%, being grade 3 in 13.3%. Other grade 3 toxicities were thrombocytopenia (6.7%), fatigue (13.3%), and nausea (6.7%). The rate of dose reductions was 53.3%, though no patients discontinued treatment.

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, noted that none of the safety data was new or unexpected, and that there are standard dose reduction guidelines to follow.

He also discussed the work of multidisciplinary clinicians, such as nurses and pharmacists, in using dose reductions by talking to patients and understanding how they are reacting to treatment. Hornstein expressed that TAS-102 is a difficult agent to take, and it requires a large time investment from patients, requiring work from everyone involved in a patient’s treatment to help mitigate toxicities related to its use.

Transcript:

TAS-102 is one of these drugs that we know requires dose reduction. It happens in the metastatic setting. It happened here. There are standard dose reduction guidelines that we use to give TAS-102 safely. That wasn’t especially challenging. It was a bit built into the treatment modality itself. It’s not like we had to figure it out on the fly.

In terms of dosing and dose reductions, both nursing and pharmacy [multidisciplinary team members] are important to watch for some of these symptoms. Some of them are lab-based, where [oncologists] are going to need to monitor them, but others are [about] talking to patients, seeing how they’re feeling, and how they are experiencing this. Are they taking the drug in the right way? TAS-102 is a bit of a pain to take—it’s on and off throughout a month—and if you don’t have somebody checking in, if you don’t have a strong nurse, pharmacy team, or [medical assistant] team that’s calling and trying to help these patients through it, there’s going to be challenges with dosing. I see it all the time, especially with patients coming in from the community [setting] where there isn’t this level of oversight. They said, “I was on TAS-102 for 30 days straight, and it was terrible.” I said, “Well, we can work on that. There are some solutions here; let’s change this around a little bit.” They have an important role there.

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