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

BACKGROUND

Hepatic artery infusion of chemotherapy has demonstrated disease control and suggested improvement in overall survival in intrahepatic cholangiocarcinoma. We report herein the long-term results and role of molecular alterations of a phase II clinical trial of hepatic artery infusion chemotherapy plus systemic chemotherapy, with a retrospective cohort of patients treated with hepatic artery infusion at Memorial Sloan Kettering Cancer Center.

METHODS

This is a secondary analysis of a single-institution, phase II trial, and retrospective cohort of unresectable intrahepatic cholangiocarcinoma treated with hepatic artery infusion floxuridine 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 overall survival.

RESULTS

A total of 38 patients were treated on trial with a median follow-up of 76.9 months. Median PFS was 11.8 months (95% confidence interval [CI] = 11 to 15.1 months). The median overall survival was 26.8 months (95% CI = 20.9 to 40.6 months). The 1-, 2-, and 5-year overall survival rate was 89.5%, 55%, and 21%, respectively. Nine (24%) patients received hepatic artery infusion with mitomycin C post-floxuridine progression with an objective response rate of 44% and a median PFS of 3.93 months (95% CI = 2.33 months to not reached). A total of 170 patients not treated on the clinical trial were included in a retrospective analysis. Median PFS and overall survival were 7.93 months (95% CI = 7.27 to 10.07 months) and 22.5 months (95% CI = 19.5 to 28.3 months), respectively. Alterations in the TP53 and cell-cycle pathway had a worse PFS to hepatic artery infusion-based therapy compared with wild-type disease.

CONCLUSION

In locally advanced intrahepatic cholangiocarcinoma, hepatic artery infusion with floxuridine in combination with systemic therapy can offer long-term durable disease control. Molecular alterations may predict for response.