Hideaki Bando, MD, PhD is a medical oncologist in the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East, in Japan.

Dr Bando on the Next Steps for Evaluating TAS-102 in MRD+ Resected CRC

Hideaki Bando, MD, PhD, a member of the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East, discussed updated safety and subgroup findings from the phase 3 ALTAIR trial (NCT04597116), which evaluated trifluridine/tipiracil (TAS-102; Lonsurf) in patients with colorectal cancer (CRC) who were minimal residual disease (MRD) positive following resection.

2025 ASCO Gastrointestinal Cancer Symposium

 showed that grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 73.0% of patients treated with TAS-102 compared with 3.3% of patients given placebo. These TEAEs were primarily hematologic, including neutropenia and leukopenia, and no new safety signals emerged. Despite the incidence of higher-grade toxicities, overall quality of life was not notably diminished, Bando noted, reinforcing the tolerability of the regimen in this clinical setting.

Bando emphasized that although TAS-102–related toxicities were not unexpected, the agent was generally manageable with supportive care and did not compromise treatment adherence. The high rate of AEs observed aligns with prior studies of TAS-102 in the metastatic CRC setting.

Importantly, Bando highlighted that exploratory subgroup analyses are underway to identify predictors of clinical benefit. Initial findings suggest that patients with higher baseline circulating tumor DNA (ctDNA) levels may experience greater therapeutic benefit from TAS-102, and those with lower ctDNA levels demonstrated more limited efficacy. This underscores the importance of stratifying patients based on molecular disease burden and refining ctDNA thresholds to optimize patient selection for future trials.

Further analysis is ongoing to evaluate mechanisms of ctDNA clearance in patients with low baseline molecular burden, with the goal of informing more precise MRD-guided treatment strategies. In particular, Bando noted that ctDNA dynamics may help identify which patients are most likely to benefit from early intervention with TAS-102 and guide trial design for future studies.

Overall, Bando concluded that the ALTAIR trial supports the feasibility of TAS-102 as a pre-emptive therapy in MRD-positive CRC after resection and provides a foundation for future prospective studies evaluating ctDNA-guided treatment decisions. Additional biomarker analyses and survival follow-up will be necessary to fully establish the clinical relevance of this approach in the adjuvant setting.

Videos

Hideaki Bando, MD, PhD, discusses the safety of trifluridine/tipiracil in patients with MRD following resection of CRC.

Dr Bando on Safety of TAS-102 in MRD+ Resected CRC

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).

 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; 

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; 

 = .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.

Hideaki Bando, MD, PhD, discusses efficacy outcomes with TAS-102 as a pre-emptive treatment in patients with MRD-positive CRC following curative resection.

Hideaki Bando, MD, PhD

Articles

Dr Bando on Safety of TAS-102 in MRD+ Resected CRC

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