Efficacy and safety of hepatic arterial infusion chemotherapy with FOLFOX or FOLFIRI plus drug-eluting bead transarterial chemoembolization in unresectable colorectal liver metastases.

Abstract

53 Background: Liver metastases are the main cause of death in colorectal cancer (CRC), yet only ~20% of patients qualify for surgery. For unresectable colorectal liver metastases (CRCLM), hepatic arterial infusion chemotherapy (HAIC) and drug-eluting bead transarterial chemoembolization (DEB-TACE) are common treatments. This study assesses the efficacy and safety of combining DEB-TACE with HAIC using FOLFOX or FOLFIRI. Methods: This retrospective study included 221 CRCLM patients treated at Peking University Cancer Hospital from 2018 to 2023. Of these, 182 received DEB-TACE with HAIC-FOLFOX and 39 with HAIC-FOLFIRI. Propensity score matching (PSM) minimized selection bias. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), hepatic PFS (hPFS), objective response rate (ORR), disease control rate (DCR), and treatment-related safety. Results: Propensity matching resulted in 38 pairs, achieving comparable baseline between DEB-TACE-HAIC-FOLFOX and DEB-TACE-HAIC-FOLFIRI cohorts. Of these pairs, 45 were male and 31 were female. Around 65.8% patients were younger than 65 years. The original locations of CRC in 67.1% of patients were on the left side. The middle to high grades of tumor were dominant (88.2%). Notably, 56.6% of patients harbored mutations in KRAS, NRAS or BRAF and extrahepatic metastasis occurred in 78.9% patients. Additionally, 75% patients were refractory to second line systemic therapy. Median hepatic progression-free survival (hPFS), progression-free survival (PFS), and overall survival (OS) were all slightly better in the matched DEB-TACE-HAIC-FOLFOX cohort, but not statistically significant (median hPFS: 8.6 vs. 5.8 months, P=0.206; median PFS: 6.4 vs. 4 months, P=0.062; median OS: 11.8 vs. 10.8 months, P=0.249). The objective response rate (ORR) was 36.8% in the DEB-TACE-HAIC-FOLFOX group and 39.5% in the DEB-TACE-HAIC-FOLFIRI group, with disease control rates (DCR) of 71.1% and 76.3%, respectively. These patients received 224 DEB-TACE plus HAIC treatments. There were no treatment-related deaths. Serious adverse events were comparable between the two groups, except for elevated transaminase. However, transaminase elevation was actually due to drug-eluting beads difference during DEB-TACE. With the further analysis of drug-eluting beads’ effect on adverse events, transaminase elevation, nausea, vomiting and pain occurred much frequently with DCB drug-eluting bead than HepaSphere drug-eluting bead; these differences were statistically significant. Conclusions: The combination of DEB-TACE with FOLFOX or FOLFIRI HAIC shows promising efficacy and tolerable safety for unresectable CRCLM. The FOLFIRI-based regimen is a viable alternative, especially for oxaliplatin-intolerant patients.