Drug-eluting beads loaded with irinotecan-transarterial chemoembolization (DEBIRI-TACE) combined with hepatic artery infusion chemotherapy and regorafenib in colorectal liver metastases refractory to second-line and above standard systemic therapy: A

3539 Background: For patients with colorectal liver metastasis (CRLM) who have failed in first-line or second-line systemic treatment, the prognosis is extremely poor. Regorafenib is the standard third line treatment regimen. We aim to explore the safety and clinical efficacy of added drug eluting beads loaded with irinotecan (DEBIRI) plus hepatic arterial infusion chemotherapy (HAIC) to regorafenib in the combination treatment of second-line and above in patients with CRLM. Methods: For this single-center, single-arm, prospective, phase II trial, patients with unresectable progression of CRLM after previously receiving at least six cycles of standard systemic chemotherapy above the second line were enrolled. All of the patients received at least once DEBIRI-TACE and FOLFOX-HAIC (Oxaliplatin 85mg/m 2 2h + Calcium Levofolinate 200mg/m 2 2h + Fluorouracil 2400mg/m 2 46h) plus oral regorafenib 80/120/160 mg once daily during weeks 1-3 of each 4-week cycle until disease progression or unacceptable toxicity. The primary endpoint of this study was the best objective response rate (ORR) per RECIST 1.1, the secondary endpoints include progression-free survival (PFS), overall survival (OS), safety and tolerability assessments. Results: By the cutoff date of 17 November 2023, 21 patients were enrolled, with the median age of 61 (ranges, 38-71 years old), 14 (66.7%) of whom were male. 17(81.0%) patients had more than one tumor and 13(61.9%) patients had major tumor larger than 5cm. The most frequent primary cancer localization was colon (81.0%) and the primary had been resected in 14(66.7%) patients. Somatic mutation status was available for 15 patients: KRAS mutation was found in 7 patients. The ORR was 33.3% and the DCR was 100%. The median PFS was 7.8 months (95% CI: 5.8–NA), the median OS was 17.6 months (95% CI: 9.3–NA), the 1-year and 2-year OS rate were 54.6% (30.7%-73.4%) and 23.9% (4.6%-51.3%), respectively, and the 1-year PFS rate was 36.4% (15.7%-57.5%). The most common TRAEs were AST/ALT increase (81.8%), abdominal pain (63.6%), hyperbilirubinemia (63.6%), hand-foot skin reaction (59.1%), diarrhea (40.9%), etc. 9 patients presented with grade 3 or 4 TRAEs, which were the transient liver function injury and abdominal pain caused by TACE and HAIC. Conclusions: DEBIRI-TACE combined with HAIC and regorafenib is feasible, safe and shows promising efficacy in treating the patients with CRLM, even after second-line and above systemic chemotherapy. Clinical trial information: NCT06071052 .