Dr Bando on Safety of 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.

Data presented at the 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.