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

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

doi:10.1093/jnci/djae202

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

J Natl Cancer Inst. 2024 Sep 27:djae202. doi: 10.1093/jnci/djae202. Online ahead of print.

Authors

Darren Cowzer¹, Kevin Soares^{1

2}, Henry Walch¹, Mithat Gönen^{1

2}, Taryn M Boucher¹, Richard K G Do^{1

2}, James J Harding^{1

2}, Anna M Varghese^{1

2}, Diane Reidy-Lagunes¹, Leonard Saltz^{1

2}, Louise C Connell^{1

2}, Ghassan K Abou-Alfa^{1

2

3}, Alice C Wei^{1

2}, Nikolaus Schultz¹, T Peter Kingham^{1

2}, Michael I D'Angelica^{1

2}, Jeffrey A Drebin^{1

2}, Vinod Balachandran^{1

2}, Francisco Sanchez-Vega¹, Nancy E Kemeny^{1

2}, William R Jarnagin^{1

2}, Andrea Cercek^{1

2}

Affiliations

¹ Memorial Sloan Kettering Cancer Center, New York, NY, United States of America.
² Weill Medical College at Cornell of University, New York, NY, United States of America.
³ Trinity College Dublin, Dublin, Ireland.

PMID: 39331613
DOI: 10.1093/jnci/djae202

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.