Multicenter phase 3 trial of post-adjuvant chemotherapy in ctDNA-positive patients after resection of colorectal cancer

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease after curative resection of colorectal cancer (CRC). The multicenter phase 3 ALTAIR trial in Japan evaluated a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with stage 0-IV CRC who became ctDNA-positive after completion of standard of care therapy and had no radiological evidence of disease were randomized 1:1 to receive trifluridine/tipiracil (FTD/TPI) or placebo for six months. The primary endpoint was investigator-assessed disease-free survival (DFS). A total of 243 patients were randomized to FTD/TPI (n=122) or placebo (n=121). Among all randomized patients, median DFS was 9.30 months in the FTD/TPI group and 5.55 months in the placebo group (HR 0.79; p=0.107); among stage IV patients the HR was 0.53 (p=0.012), whereas no significant benefit was detected among stage I-III patients (HR 0.86; p=0.375). FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. The authors conclude that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease.