Zanidatamab-hrii Extends Survival in Previously Treated HER2-Positive BTC

Biliary tract cancer (BTC), a rare and aggressive malignancy, has limited treatment options, particularly for patients with advanced or metastatic disease who have progressed after using a first-line therapy such as a gemcitabine-containing regimen. HER2-positive BTC, a subset of these cancers, presents a potential target for therapeutic intervention. Zanidatamab-hrii, a bispecific HER2-directed antibody, was recently evaluated in the phase 2 HERIZON-BTC-01 trial (NCT04466891) and demonstrated promising efficacy in this challenging disease setting. To further contextualize these results, a real-world external control arm (ECA) was constructed to compare the outcomes of zanidatamab-hrii with second-line chemotherapy in a similar patient population.

The HERIZON-BTC-01 trial included patients with HER2-positive, confirmed through immunohistochemistry, unresectable, locally advanced, or metastatic BTC who had previously been treated with a gemcitabine-containing regimen. In this study, patients from the HERIZON-BTC-01 trial received zanidatamab at 20 mg/kg intravenously every 2 weeks. The real-world ECA was built using deidentified data from the Flatiron Health Electronic Health Record database, which included patients with a diagnosis of gallbladder cancer or intrahepatic cholangiocarcinoma/extrahepatic cholangiocarcinoma confirmed HER2-positive disease, and initiation of second-line chemotherapy. Standardized mortality ratio weighting was applied to balance the baseline characteristics between the 2 groups. Baseline variables for ECA weighing were age at second-line initiation, sex, disease subtype, and history of chronic liver disease.

A total of 62 patients were in the zanidatamab cohort. In the ECA cohort, 290 patients with advanced or metastatic BTC who were on second-line treatment were identified. Two hundred seventy-eight patients were excluded, and 12 patients were included in the ECA after eligibility criteria were applied. The results demonstrated that zanidatamab-hrii significantly extended both overall survival (OS) and progression-free survival (PFS) compared with second-line chemotherapy. Median OS for patients receiving zanidatamab-hrii was 18.1 months compared with 3.3 months observed in the ECA. Similarly, median PFS was 7.3 months for zanidatamab-hrii compared with 2.3 months in the ECA group. Six-month OS rates were 90% for zanidatamab-hrii patients compared with 29% for the ECA, and 12-month OS rates were 65% compared with 13%, respectively. The PFS rates at 6 months were 55% for zanidatamab-hrii patients and 14% for the ECA, with 12-month PFS rates of 32% and 14%, respectively.

In conclusion, zanidatamab-hrii demonstrated significant survival benefits over standard chemotherapy in previously treated HER2-positive BTC patients, with a median OS improvement of >14 months. These results support the potential of zanidatamab-hrii as a transformative option for this aggressive cancer type, paving the way for its broader application in clinical practice. This study reinforces the importance of targeted therapies in addressing the unique challenges posed by HER2-positive BTC and offers new hope for patients with limited treatment options.

Source:

Kim RD, Fan X, Sabater J, et al. Survival outcomes for zanidatamab-hrii compared to chemotherapy in previously treated HER2-positive (IHC3+) biliary tract cancer (BTC): HERIZON-BTC-01 vs a real-world (RW) external control arm (ECA). Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Poster 391.