FOLFOX-based hepatic arterial infusion chemotherapy combined with regorafenib for unresectable colorectal liver metastases.

e15601 Background: Hepatic arterial infusion chemotherapy (HAIC) stands out as a compelling local therapeutic strategy for patients with unresectable colorectal liver metastases (CRLM). Meanwhile, regorafenib has established itself as a systemic treatment for CRLM. The potential synergistic antitumor effect of combining HAIC and regorafenib in the treatment of unresectable CRLM remains intriguing, yet clinical evidence supporting the efficacy of this combination therapy is lacking. This study aims to evaluate the safety profile and therapeutic benefit of FOLFOX-HAIC plus regorafenib in the management of unresectable CRLM. Methods: In this retrospective analysis, we included 35 patients with unresectable CRLM who underwent FOLFOX-HAIC plus regorafenib between July 2020 and January 2023. The mFOLFOX6 regimen was employed for HAIC, comprising oxaliplatin (85 mg/m 2 for 2 h on day 1), calcium folinate (200 mg/m 2 for 2 h on day 1), and 5-fluorouracil (5-Fu) administered as a bolus of 400 mg/m 2 on day 1, followed by 2400 mg/m 2 over 46 h. Regorafenib was administered orally at a dose of 160 mg (four 40 mg tablets) once daily for the first 21 days of each 28-day cycle, with HAIC performed during the 7 days of discontinuation. The primary outcome was overall survival (OS), and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR) and adverse events (AEs). Factors affecting the OS were also analyzed. Results: Kaplan-Meier analyses revealed a median OS of 29.0 months (95% confidence interval CI, 17.9-40.1) and a median PFS of 13.0 months (95% CI, 9.3-16.7). Post-HAIC ORRs at 3, 6, and 12 months were 71.4%, 80.0%, and 57.2%, respectively, while DCRs were 88.6%, 91.4%, and 74.3%. In univariable and multivariable Cox regression models, ascites (HR = 5.640, 95%CI: 1.204-30.176, P = 0.033) and carcinoembryonic antigen levels > 10μg/L (HR = 11.49, 95%CI: 1.232-88.758, P = 0.012) emerged as independent prognostic factors for OS. AEs associated with HAIC encompassed nausea, vomiting, abdominal pain, and fever. In the context of regorafenib, the prevailing AEs included hand-foot skin reactions and hypertension. Importantly, during the follow-up period, no life-threatening AEs were reported in patients receiving HAIC or regorafenib. Conclusions: The combination of regorafenib with FOLFOX-HAIC exhibits substantial promise in managing unresectable CRLM, providing meaningful effectiveness without exacerbating toxicity. Table: see text