Preoperative versus Postoperative chemotherapy with CAPOX plus bevacizumab for resectable colorectal liver metastases: A randomised phase II trial (HiSCO-01)

Abstract

Abstract Background NCCN and ESMO guidelines recommend 6 months of perioperative oxaliplatin-based chemotherapy for patients with resectable colorectal liver metastases (CRLM). However, the optimal sequencing and chemotherapy regimen remain unclear. Methods We conducted a randomised phase II trial, HiSCO-01, to compare the outcomes of preoperative (Preop-group) and postoperative chemotherapy (Postop-group) with eight cycles of CAPOX plus bevacizumab (CAPOX-Bev) in patients with resectable CRLM. The primary endpoint was the treatment completion rate (TCR), defined as the percentage of patients who received at least six cycles of CAPOX-Bev and underwent R0 resection. Results Of the 81 patients enrolled, 76 patients were eligible. The TCR was 89.2% in the Preop-group and 71.8% in the Postop-group (p = 0.06). The overall incidence of chemotherapy-related grade 3 or higher adverse events was similar between the two groups. The postoperative complications rate was comparable except that biliary fistula developed significantly higher in the Postop-group. The 3-year progression-free survival and 5-year overall survival rates were 32.2% and 60.5% in the Preop-group, respectively, and 38.5% and 57.2% in the Postop-group, respectively. Conclusion Eight cycles of CAPOX-Bev before R0 resection for resectable CRLM is feasible and safe. However, the survival benefits of preoperative chemotherapy over postoperative chemotherapy remain unproven. Trial registration: This trial was registered in the UMIN Clinical Trial Registry (UMIN000003783) and was coordinated centrally by the Hiroshima Surgical Study group of Clinical Oncology (HiSCO).