Real-world efficacy of zanidatamab in patients with HER2 positive advanced biliary tract cancers

Introduction: 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. Patients & methods: 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. Results: 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. Conclusion: The benefits of in patients with HER2-positive BTC were confirmed. Zanidatamab should be considered for patients with this condition.