https://orcid.org/0000-0002-0969-3259
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Darren Cowzer, Kevin Soares, Henry Walch, Mithat Gönen, Taryn M Boucher, Richard K G Do, James J Harding, Anna M Varghese, Diane Reidy-Lagunes, Leonard Saltz, Louise C Connell, Ghassan K Abou-Alfa, Alice C Wei, Nikolaus Schultz, T Peter Kingham, Michael I D’Angelica, Jeffrey A Drebin, Vinod Balachandran, Francisco Sanchez-Vega, Nancy E Kemeny, William R Jarnagin, Andrea Cercek, Long-term outcomes in patients with advanced intrahepatic cholangiocarcinoma treated with hepatic arterial infusion chemotherapy, JNCI: Journal of the National Cancer Institute, Volume 117, Issue 2, February 2025, Pages 279–286, https://doi.org/10.1093/jnci/djae202
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Abstract
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.
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.
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.
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.
