Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Journal article

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0-IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60-1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 .

Authors: Bando, H; Watanabe, J; Takahashi, Y; Kotaka, M; Matsuhashi, N

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Medicine
• Publication date: 2026-06-08
• Acceptance date: 2026-04-28
• DOI: 10.1038/s41591-026-04428-0
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English
• Keywords: Stage (stratigraphy); Placebo; Clinical endpoint; Randomized controlled trial; Chemotherapy; Adverse effect; Colorectal cancer