Dr Bando on Benefit With TAS-102 in Select Patients With MRD-Positive CRC Following Curative Resection

“We can confirm the efficacy of [TAS-102]. Unfortunately, clinical significance [with TAS-102 in the primary study population] was not shown in this study. However, when we focused on stage IV patients that have higher circulating tumor DNA levels, [TAS-102 did] show a clinically significant [DFS benefit over placebo.]”

Hideaki Bando, MD, PhD, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, discusses the clinical relevance of using trifluridine/tipiracil (TAS-102) as a pre-emptive treatment in patients with molecular residual disease (MRD) following curative resection of colorectal cancer (CRC), according to findings from the phase 3 ALTAIR trial (NCT04457297).

Results presented at the 2025 ASCO Gastrointestinal Cancer Symposium demonstrated a numerical improvement in disease-free survival (DFS) with TAS-102 compared with placebo, though statistical significance was not reached in the primary population (n = 243), Bando reports. The median DFS was 9.30 months with TAS-102 vs 5.55 months with placebo (HR, 0.79; 95% CI, 0.60-1.05; P = .107).

However, in the subset of patients with resected stage IV oligometastatic disease (n = 66), the benefit with TAS-102 was more pronounced, Bando details. In this high-risk patient population, the median DFS was 9.76 months with TAS-102 vs 3.96 with chemotherapy, suggesting clinical relevance (HR, 0.53; 95% CI, 0.32-0.87; P = .012), Bando emphasizes. Additionally, a trend toward greater DFS benefit was observed with increasing mean tumor molecule values at baseline, which were used to evaluate circulating tumor DNA levels, he notes.

Overall survival data remain immature, with only 24 events recorded across both treatment arms. Safety data indicated a high rate of grade 3 or higher adverse effects in the TAS-102 arm (73.0%) compared with the placebo arm (3.3%), which is consistent with the known safety profile of the agent. Further analyses and presentations will provide additional insights into whether specific subgroups of patients with MRD-positive CRC could derive a more significant benefit from TAS-102, Bando concludes.