Hepatic Arterial Infusion Pump Chemotherapy in Patients With Unresectable Intrahepatic Cholangiocarcinoma—PUMP-2 Trial

Abstract

PURPOSE The 3-year overall survival (OS) for advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver after systemic chemotherapy with gemcitabine-cisplatin (gem-cis) is only 3%. Hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine aims to control the liver disease and improve survival. The aim of this study was to assess the effectiveness of HAIP chemotherapy with floxuridine and concurrent systemic gem-cis in patients with unresectable liver-confined iCCA in the Netherlands. METHODS We performed a nonrandomized multicenter phase II trial. Treatment-naïve patients and patients previously treated with systemic therapy were eligible. Up to six cycles of HAIP floxuridine and eight cycles of concurrent systemic gem-cis were administered. The primary endpoint was 1-year OS compared with a historical cohort. RESULTS From January 2020 to September 2022, 50 patients had a pump placed. Two patients (4%) did not start HAIP floxuridine; one patient died due to COVID-19, and one patient had a hepatic arterial dissection. The remaining 48 patients (96%) started HAIP chemotherapy, combined with systemic gem-cis in the 37 patients (74%) who had not received gem-cis previously. Twenty-two patients (44%) achieved a partial response and 42 patients (84%) disease control at 6 months. Five patients (10%) converted to resection, of whom one had a complete pathologic response. The median OS was 22.3 months (95% CI, 19.7 to 35.9 months). The 1-year OS of 80.0% (95% CI, 69.6% to 91.9%) was superior to the historical control of 47% ( P < .001). The 3-year OS was 31.5% (95% CI, 20.4% to 48.6%). CONCLUSION Combining HAIP chemotherapy with floxuridine and systemic gem-cis in patients with unresectable liver-confined iCCA had a 1- and 3-year OS superior to gem-cis alone in historical cohorts.