Postoperative chemotherapy reintroduction in good responders after colorectal liver metastases resection: A French randomized phase III trial - IRIMAD.

Most patients who develop metachronous colorectal liver metastases (CRLM) have previously received adjuvant FOLFOX for stage III primary cancer. Perioperative FOLFOX is often contraindicated due to persistent neuropathy or suspected oxaliplatin resistance, leading most of these patients to receive preoperative FOLFIRI±a VEGF/EGFR-targeting biologic. The benefit of reintroducing FOLFIRI as adjuvant treatment in good responders has never been evaluated. This is a multicentre, open-label, randomised, two-arm, phase III superiority trial.

Eligible patients who underwent curative (R0/R1) resection of fewer than 10 metachronous CRLM showing objective response after 2-8 cycles of preoperative FOLFIRI will be randomised to postoperative FOLFIRI reintroduction (experimental arm, 4-10 cycles to reach a total of 12 perioperative cycles) or no postoperative treatment (control arm). The primary endpoint is 3-year disease-free survival. Secondary endpoints include overall survival, liver-free survival, extra-hepatic recurrence rate, compliance, quality of life, and treatment-related toxicity. The required sample size is 254 patients (127 per arm).

Currently, patients treated with preoperative FOLFIRI receive no adjuvant chemotherapy, as trials failed to show benefit in unselected populations. Demonstrating efficacy of adjuvant FOLFIRI in good responders would validate the concept of tailored postoperative treatment based on chemotherapy response. ClinicalTrials.gov NCT06501482 (07/2024). https://clinicaltrials.gov/study/NCT06501482.