Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial.
Bando H., Watanabe J., Takahashi Y., Kotaka M., Matsuhashi N., Oki E., Komatsu Y., Shiozawa M., Hirata K., Miyamoto Y., Takahashi M., Yamazaki K., Manaka D., Kanazawa A., Liang Y-H., Yeh K-H., Watsuji Y., Yamamoto Y., Fukui M., Sharma S., Aushev VN., Jurdi A., Rabinowitz M., Liu MC., Aleshin A., Takemasa I., Kotani D., Sato A., Misumi T., Nakamura Y., Shi Q., Taniguchi H., Yoshino T., Kato T.
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 .