Post-hoc central radiological review of the ALTAIR study in patients with molecular residual disease (MRD) following curative resection of colorectal cancer (CRC).

Abstract

138 Background: Tumor-informed circulating tumor DNA (ctDNA) testing is recognized as a powerful predictor of CRC recurrence. The randomized, double-blind, phase III ALTAIR study (NCT04457297) enrolled MRD-positive patients with CRC who had undergone curative resection of primary and/or metastatic sites + standard of care adjuvant treatment if applicable. Trifluridine/tipiracil (FTD/TPI) demonstrated a numerically longer median disease-free survival (DFS) compared with placebo (9.3 vs 5.5 months), although the difference did not reach statistical significance (P=0.107). We conducted a post-hoc independent blinded central radiological review with a panel of four expert radiologists to confirm these findings. Methods: Blinded central radiology review was conducted according to the predefined review charter. For each patient, the baseline scan, the scan at the time of recurrence as determined by the local investigator, and other scans deemed necessary for evaluation were reviewed. Each case was first assessed by one independent radiologist (single-reader approach). When findings were discordant with the local investigator’s assessment, or when consensus was judged necessary, additional review by another radiologist and panel discussion were undertaken to reach a final determination. All reviewers were blinded to clinical information other than the prespecified imaging data, as well as to ctDNA results and treatment allocation. Results: Of the 243 patients enrolled in ALTAIR, 242 had imaging (CT/MRI/PET/US) available, which was included in the central review. The central review reclassified 4 cases initially judged as non-recurrence into recurrence and 6 cases initially judged as recurrence into non-recurrence. Based on the central review, DFS analysis demonstrated a statistically significant benefit of FTD/TPI over placebo in all patients (median DFS 9.23 vs 5.55 months; HR: 0.75, 95% CI: 0.55-0.98; P=0.0406). Conclusions: Although exploratory in nature, this post-hoc analysis with central radiological review resulted in a statistically significant DFS benefit with FTD/TPI in patients with MRD-positive CRC post-definitive treatment. This stresses the importance of pre-specified blinded independent central radiological review in clinical trials for which documentation of recurrence/progression is critical to the primary analysis. Clinical trial information: NCT04457297 .