Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial.
Journal
Nature medicine
Journal Volume
32
Journal Issue
7
ISSN
1546-170X
Date Issued
2026-07
Author(s)
Bando, Hideaki
Watanabe, Jun
Takahashi, Yusuke
Kotaka, Masahito
Matsuhashi, Nobuhisa
Oki, Eiji
Komatsu, Yoshito
Shiozawa, Manabu
Hirata, Keiji
Miyamoto, Yuji
Takahashi, Masanobu
Yamazaki, Kentaro
Manaka, Dai
Kanazawa, Akiyoshi
Liang, Yi-Hsin
Watsuji, Yuko
Yamamoto, Yuko
Fukui, Makoto
Sharma, Shruti
Aushev, Vasily N
Jurdi, Adham
Rabinowitz, Matthew
Liu, Minetta C
Aleshin, Alexey
Takemasa, Ichiro
Kotani, Daisuke
Sato, Akihiro
Misumi, Toshihiro
Nakamura, Yoshiaki
Shi, Qian
Taniguchi, Hiroya
Yoshino, Takayuki
Kato, Takeshi
Abstract
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 .
Type
journal article