The phase 3 ALTAIR study has revealed promising results for Lonsurf (trifluridine/tipiracil) in treating stage 4 colorectal cancer patients with molecular residual disease following curative resection, despite missing its primary endpoint in the overall study population.
Significant Benefits in Stage 4 Disease
In the stage 4 patient subgroup, Lonsurf demonstrated a marked improvement in disease-free survival (DFS), achieving a median of 9.76 months compared to 3.96 months with placebo. The six-month DFS rates were particularly striking, with 70.47% for Lonsurf-treated patients versus 31.25% for those receiving placebo.
The study, presented at the 2025 Gastrointestinal Cancers Symposium, showed that while the overall population's median DFS was 9.3 months with Lonsurf compared to 5.55 months with placebo, this difference did not reach statistical significance.
Study Design and Patient Characteristics
The ALTAIR trial enrolled 243 patients who had undergone curative resection and tested positive for circulating tumor DNA (ctDNA). The study population was well-balanced, with 64% of patients under 70 years, 58% male, and 71% having left-sided colon as their primary tumor site. Notable molecular characteristics included 96% BRAF wild-type disease and 98% microsatellite-stable disease.
Biomarker-Based Insights
A key finding emerged regarding baseline minimal tumor markers (MTM/mL), which were significantly elevated in stage 4 patients (0.68) compared to non-stage 4 patients (0.32). Dr. Hideaki Bando and colleagues from the National Cancer Center Hospital East in Kashiwa, Japan, noted that Lonsurf's benefit showed a linear correlation with increasing MTM/mL values at enrollment.
Safety Profile
The safety assessment revealed that 98.4% of Lonsurf-treated patients experienced side effects, with 73% experiencing grade 3 or worse adverse events. This contrasted with the placebo group, where 57% reported any-grade side effects and only 3.3% experienced severe adverse events. Treatment discontinuation due to side effects occurred in 6.6% of Lonsurf-treated patients, with no fatal adverse events reported in either arm.
Clinical Implications
These findings suggest a potential new approach for treating molecular residual disease in colorectal cancer, particularly for stage 4 patients. The study builds on previous research showing ctDNA testing as a strong predictor for colorectal cancer recurrence, offering a possible pre-emptive therapy strategy for patients with positive ctDNA following curative surgery.
Overall survival data remains immature with only 24 events observed across both treatment arms, indicating the need for longer follow-up to fully understand the treatment's impact on patient survival.
