In the HERIZON BTC 01 trial for patients with HER2-positive biliary tract cancer (BTC) previously treated with systemic therapy, zanidatamab improved the objective response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). However, real-world data are needed to assess its efficacy and safety outside clinical trials.

We conducted an investigator initiated national multicenter retrospective study of most patients with BTC treated with zanidatamab in France as part of a compassionate access. The primary endpoint was PFS.

Our study included 20 patients with metastatic BTC enrolled between September 2022 and November 2024. The median age at diagnosis was 61.5 (interquartile range: 55-69) years and the majority of patients had gallbladder cancer (n = 12, 60 %). After a median follow-up of 8.5 (95 % confidence interval [CI]: 3.3-11.8) months, the median PFS was 6.7 (95 % CI 1.3-11.8) months, with an estimated OS at 1 year of 79.1 % (95 % CI: 53.2-91.6 %). The DCR was 65 %, with 40 % confirmed partial responses and a median duration of response of 7.3 (95 % CI: 2.06-16) months. Patients with immunohistochemistry (IHC) 3 + HER2 scores had a better PFS [8 (95 % CI: 1.5-18.4) months] than those with 2 + HER2 scores obtained by IHC followed by fluorescence in situ hybridization amplification or next-generation sequencing [1.4 (95 % CI: 1.1-6.8) months] (P = 0.02). No statistical difference in 1-year estimated OS rates was observed (P = 0.39). There were no grade 3 or 4 treatment-related adverse events or cardiac toxicities.

The benefits of in patients with HER2-positive BTC were confirmed. Zanidatamab should be considered for patients with this condition.