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Peer-reviewedCC BY-NC-NDNature Medicine

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

  • Hideaki Bando1,2,3
  • Jun Watanabe4,5
  • Yusuke Takahashi6
  • Masahito Kotaka7
  • Nobuhisa Matsuhashi8
  • Eiji Oki9
  • Yoshito Komatsu10
  • Manabu Shiozawa11
  • Keiji Hirata12
  • Yuji Miyamoto13
  • Masanobu Takahashi14
  • Kentaro Yamazaki15
22 more authors
  • Dai Manaka16
  • Akiyoshi Kanazawa17
  • Yi-Hsin Liang18
  • Kun‐Huei Yeh18
  • Yuko Watsuji19
  • Yuko Yamamoto19
  • Makoto Fukui20
  • Shruti Sharma21
  • Vasily N. Aushev21
  • Adham Adel Jurdi21
  • Matthew Rabinowitz21
  • MC Liu21
  • Alexey A. Aleshin21
  • Ichiro Takemasa22
  • Daisuke Kotani2
  • Akihiro Sato20
  • Toshihiro Misumi1
  • Yoshiaki Nakamura23,3
  • Qian Shi24
  • Hiroya Taniguchi25
  • Takayuki Yoshino26,27,28
  • Takeshi Kato6
28 affiliations
  1. 1Department of Data Science, National Cancer Center Hospital East, Kashiwa, Japan
  2. 2Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
  3. 3Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan
  4. 4Department of Colorectal Surgery, Kansai Medical University, Osaka, Japan
  5. 5Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
  6. 6Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
  7. 7Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan
  8. 8Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University, Graduate School of Medicine. Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu, Japan
  9. 9Department of Advanced Medicine and Innovative Technology, Kyushu University Hospital, Fukuoka, Japan
  10. 10Department of Cancer Center, Hokkaido University Hospital, Sapporo, Japan
  11. 11Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Japan
  12. 12Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  13. 13Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
  14. 14Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
  15. 15Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
  16. 16Department of Surgery, Gastro-Intestinal Center, Kyoto Katsura Hospital, Kyoto, Japan
  17. 17Department of Surgery Shimane Prefectural Central Hospital, Shimane, Japan
  18. 18Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
  19. 19EPS Corporation, Tokyo, Japan
  20. 20Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan
  21. 21Oncology, Natera, Inc., Austin, TX, USA
  22. 22Department of Surgery, Osaka International Medical & Science Center, Osaka, Japan
  23. 23Department of Oncology, University of Oxford, Oxford, UK
  24. 24Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
  25. 25Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
  26. 26Department of Data Science, National Cancer Center Hospital East, Kashiwa, Japan. [email protected]
  27. 27Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. [email protected]
  28. 28Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan. [email protected]
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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 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

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Cite

BibTeXRIS
BibTeX
@article{bando2026postadjuvant,
  title = {{Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial}},
  author = {Hideaki Bando and Jun Watanabe and Yusuke Takahashi and Masahito Kotaka and Nobuhisa Matsuhashi and Eiji Oki and Yoshito Komatsu and Manabu Shiozawa and Keiji Hirata and Yuji Miyamoto and Masanobu Takahashi and Kentaro Yamazaki and Dai Manaka and Akiyoshi Kanazawa and Yi-Hsin Liang and Kun‐Huei Yeh and Yuko Watsuji and Yuko Yamamoto and Makoto Fukui and Shruti Sharma and Vasily N. Aushev and Adham Adel Jurdi and Matthew Rabinowitz and MC Liu and Alexey A. Aleshin and Ichiro Takemasa and Daisuke Kotani and Akihiro Sato and Toshihiro Misumi and Yoshiaki Nakamura and Qian Shi and Hiroya Taniguchi and Takayuki Yoshino and Takeshi Kato},
  journal = {Nature Medicine},
  year = {2026},
  month = jun,
  doi = {10.1038/s41591-026-04428-0},
  url = {https://doi.org/10.1038/s41591-026-04428-0},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial
AU  - Hideaki Bando
AU  - Jun Watanabe
AU  - Yusuke Takahashi
AU  - Masahito Kotaka
AU  - Nobuhisa Matsuhashi
AU  - Eiji Oki
AU  - Yoshito Komatsu
AU  - Manabu Shiozawa
AU  - Keiji Hirata
AU  - Yuji Miyamoto
AU  - Masanobu Takahashi
AU  - Kentaro Yamazaki
AU  - Dai Manaka
AU  - Akiyoshi Kanazawa
AU  - Yi-Hsin Liang
AU  - Kun‐Huei Yeh
AU  - Yuko Watsuji
AU  - Yuko Yamamoto
AU  - Makoto Fukui
AU  - Shruti Sharma
AU  - Vasily N. Aushev
AU  - Adham Adel Jurdi
AU  - Matthew Rabinowitz
AU  - MC Liu
AU  - Alexey A. Aleshin
AU  - Ichiro Takemasa
AU  - Daisuke Kotani
AU  - Akihiro Sato
AU  - Toshihiro Misumi
AU  - Yoshiaki Nakamura
AU  - Qian Shi
AU  - Hiroya Taniguchi
AU  - Takayuki Yoshino
AU  - Takeshi Kato
PY  - 2026
DA  - 2026/06/08
JO  - Nature Medicine
DO  - 10.1038/s41591-026-04428-0
UR  - https://doi.org/10.1038/s41591-026-04428-0
AB  - 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 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.
SN  - 1078-8956
SN  - 1546-170X
SN  - 1744-7933
ER  -