Long term outcomes in patients with advanced intrahepatic cholangiocarcinoma treated with hepatic arterial infusion chemotherapy

Abstract Introduction Hepatic artery infusion (HAI) of chemotherapy has demonstrated disease control and suggested improvement in overall survival (OS) in intrahepatic cholangiocarcinoma (IHC). We report herein the long-term results and role of molecular alterations of a phase II clinical trial of HAI chemotherapy plus systemic chemotherapy, with a retrospective cohort of patients treated with HAI at Memorial Sloan Kettering Cancer Center. Methods This secondary analysis of a single-institution, phase 2 trial and retrospective cohort of unresectable IHC treated with HAI floxuridine (FUDR) plus systemic gemcitabine and oxaliplatin. The primary aim was to assess long-term oncologic outcomes. A subset underwent tissue-based genomic sequencing, and molecular alterations were correlated with progression-free survival (PFS) and OS. Results Thirty-eight patients were treated on trial with a median follow up of 76.9 months. Median PFS was 11.8 months (95% CI11-15.1). The median OS was 26.8 months (95% CI20.9-40.6). The 1-, 2- and 5-year OS rate was 89.5%, 55%, and 21% respectively. Nine (24%) received HAI with mitomycin C post FUDR progression with an objective response rate of 44% and a median PFS of 3.93 (2.33-NR) months. One-hundred and seventy patients not treated on the clinical trial were included in a retrospective analysis. Median PFS and OS was 7.93 (95%CI: 7.27-10.07) and 22.5 (95%CI : 19.5-28.3) months, respectively. Alterations in the TP53 and cell-cycle pathway had a worse PFS to HAI based therapy compared to wildtype disease. Conclusion In locally advanced IHC, HAI with FUDR in combination with systemic therapy can offer long term durable disease control. Molecular alterations may predict for response.