Hepatic artery infusion pump chemotherapy for unresectable intrahepatic cholangiocarcinoma: Pooled individual patient-level analysis of four clinical trials.

BACKGROUND & AIMS: Systemic therapy is the standard of care for unresectable intrahepatic cholangiocarcinoma (iCCA), but overall survival (OS) remains poor. Hepatic artery infusion pump (HAIP) chemotherapy with floxuridine (FUDR) has been shown to prolong survival but is limited to expert centers. We assessed long-term OS among patients with unresectable, liver-confined iCCA treated with HAIP chemotherapy.

METHODS

Individual patient data from four phase II trials were pooled, including 142 patients with unresectable, liver-confined iCCA, with or without resectable regional lymph node metastases. Patients received HAIP chemotherapy with FUDR, with or without systemic therapy. The primary outcome was OS. Cox models examined associations between preselected covariates and OS.

RESULTS

Multifocal disease was found in 92 patients (65%) and 58 (41%) had tumors larger than 10 cm. Twenty-five patients (18%) received prior systemic treatment. Partial response on imaging was achieved in 73/139 patients (53%), with a disease control rate of 96%. Thirteen patients (9%) underwent resection; four achieved complete pathological response. The pooled median OS was 26 months (95% CI 22-30), with 3-year and 5-year OS rates of 28% (95% CI 22-37) and 15% (95% CI 10-23), respectively. OS was similar across trials (p = 0.95). The intention to treat 3-year and 5-year OS rates were 26% and 14%, respectively, which included 12 patients (7.8%) who did not undergo HAIP chemotherapy due to peritoneal disease. Hepatic disease progression was independently associated with worse OS (hazard ratio 4.46; 95% CI 2.69-7.40; p <0.001).

CONCLUSIONS

Patients with unresectable, liver-confined iCCA who underwent HAIP with systemic chemotherapy had a 3-year OS rate of 28% and 5-year OS rate of 15% across four phase II trials. These results provide long-term benchmark results for a selected patient population.

IMPACT AND IMPLICATIONS: Unresectable, locally advanced intrahepatic cholangiocarcinoma remains a disease with poor long-term survival, and evidence supporting liver-directed strategies is limited to small, heterogeneous single-arm studies. By pooling individual patient data from all prospective phase II trials of hepatic artery infusion pump chemotherapy with extended follow-up, this study provides the most comprehensive and mature long-term survival benchmarks. These findings will inform multidisciplinary decision-making at specialized centers and support further prospective evaluation of hepatic artery infusion pump chemotherapy within modern multimodality treatment strategies.