Trifluridine/tipiracil (Lonsurf) demonstrated a statistically significant improvement in disease-free survival (DFS) compared to placebo in patients with resected stage IV colorectal cancer (CRC) who had molecular residual disease. The findings, presented at the 2025 Gastrointestinal Cancers Symposium, come from a subgroup analysis of the phase 3 ALTAIR study (NCT04457297). While the overall study population did not show a statistically significant DFS benefit, the stage IV subgroup experienced a clinically meaningful advantage.
ALTAIR Study Details
The ALTAIR trial was designed to assess the efficacy of trifluridine/tipiracil as a preemptive treatment in patients with CRC who had undergone curative resection and tested positive for circulating tumor DNA (ctDNA), indicating molecular residual disease. The study enrolled patients from the CIRCULATE-Japan study (UMIN000039205). Patients were randomized to receive either trifluridine/tipiracil or placebo for 6 months, with regular CT and ctDNA analyses to monitor disease recurrence. The primary endpoint was DFS.
Efficacy Results
In the overall study population, trifluridine/tipiracil showed a numerical, but not statistically significant, improvement in median DFS compared to placebo (9.30 months vs 5.55 months; HR, 0.79; 95% CI, 0.60-1.05; P = .107). However, the subgroup of patients with stage IV disease experienced a significant benefit. The median DFS in the stage IV subgroup was 9.76 months with trifluridine/tipiracil compared to 3.96 months with placebo (HR, 0.53; 95% CI, 0.32-0.87; P = .012).
Specifically, the 6-, 12-, 18-, and 24-month DFS rates in the trifluridine/tipiracil arm for stage IV disease were 70.47%, 27.57%, 9.19%, and 4.60%, respectively. In the placebo arm, the corresponding rates were 31.25%, 12.5%, 3.12%, and not reached.
Safety Profile
Treatment with trifluridine/tipiracil was associated with a higher incidence of adverse events (AEs) compared to placebo. Any-grade AEs occurred in 98.4% of patients in the trifluridine/tipiracil arm vs 57% in the placebo arm. Grade 3 or higher AEs were also more frequent in the trifluridine/tipiracil arm (73.0% vs 3.3%). Serious AEs were reported in 4.9% of patients receiving trifluridine/tipiracil, while none occurred in the placebo arm. Discontinuation due to AEs occurred in 6.6% of patients in the trifluridine/tipiracil arm. No fatal AEs were reported in either arm. The study authors noted that no new safety signals were identified.
Expert Commentary
According to lead study author Hideaki Bando, MD, PhD, of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, overall survival data were immature at the time of the analysis, with only 24 events observed across both arms.
Baseline Characteristics
Baseline characteristics were well-balanced between the two treatment groups. The majority of patients had received standard-of-care treatment prior to enrollment (96.3%). In the overall population, 64% were younger than 70 years, 58% were male, 71% had left-sided colon tumors, and 45% had stage III disease. A significant proportion of patients had received neoadjuvant (36%) or adjuvant (46%) treatment. Most patients had BRAF wild-type (96%) and RAS wild-type (61%) disease, and 98% had microsatellite-stable disease.
