The overexpression of HER2 plays a significant role in the pathogenesis and advancement of some biliary tract cancers (BTCs), often resulting in a poor prognosis for these patients; however, recent developments in HER2-targeted therapies have demonstrated encouraging outcomes in HER2-positive BTC. Nevertheless, information regarding the prevalence of HER2 positivity and its influence on the prognosis of cholangiocarcinoma (CCA) patients is still scarce.
A retrospective cohort study, presented at the 2025 ASCO Gastrointestinal Cancers Symposium, investigated the impact of HER2 positivity on prognosis and treatment outcomes in advanced BTC. This study was conducted across Yonsei Cancer Center (YCC) and The University of Texas MD Anderson Cancer Center and included patients who were classified as HER2-positive based on immunohistochemistry (IHC 3+ or 2+/ISH+) or next-generation sequencing (NGS). Of the 310 patients from YCC with available HER2 IHC results, 78 were HER2-positive and 232 were HER2-negative. HER2 positivity was significantly more common in gallbladder cancer (55.1%) compared with intrahepatic (25.6%) or extrahepatic (16.7%) CCA. Among the 78 patients with NGS data, 59 (78.6%) were HER2-positive by IHC, 7 (8.9%) were positive for ERBB2 amplification, and 12 (15.5%) were positive for ERBB2 amplification and were HER2-IHC positive.
Survival analysis revealed a trend toward shorter overall survival (OS) in HER2-positive patients compared with HER2-negative patients (median OS, 13.7 vs 17.1 months; P=.084), regardless of exposure to HER2-targeted therapy. The first-line progression-free survival on chemotherapy alone was significantly shorter in the HER2-positive group (5.1 vs 7.4 months; P<.001).
HER2-positive patients who did not receive HER2-targeted therapy had a significantly poorer prognosis compared with HER2-negative patients (median OS, 8.1 vs 17.1 months). However, HER2-positive patients who did receive HER2-targeted therapy had comparable OS to HER2-negative patients (median OS, 18.2 vs 17.1 months).
This study underscores the significant role of HER2 positivity as a negative prognostic factor in advanced BTC. However, the findings also suggest that HER2-targeted therapies can improve outcomes for patients with HER2-positive tumors. These findings support the potential inclusion of HER2-targeted therapies as part of standard care for HER2-positive BTC subgroups.
Lee C, Seo DH, Fox DA, et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Presented at: ASCO Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA; Virtual. Poster E5.
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