Long term outcomes in patients with advanced intrahepatic cholangiocarcinoma treated with hepatic arterial infusion chemotherapy.
Academic Article
Overview
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.
