498 Background: ERBB2 gene amplification or HER2 receptor overexpression is a well-known oncogenic driver and represents a therapeutic target in biliary tract cancer (BTC). We aimed to describe the epidemiology of a cohort of BTC patients (pt) according to HER2 status, treatment patterns and efficacy outcomes. Methods: We evaluated a real-world pt cohort from the Spanish RETUD registry, diagnosed with BTC from January 1st, 2017, to May 30th, 2025. Pt populations were defined as resectable disease (RD) for pt with neoadjuvant/adjuvant systemic therapy (ST) and/or radical treatment (surgery and/or locoregional treatment); and advanced disease (AD) for RC pt who experienced tumor relapse and those initially treated with first line ST. ERBB2/HER2 status was assessed by next-generation sequencing (NGS), immunohistochemistry (IHC), and/or fluorescence/chromogenic in situ hybridization (FISH/CISH). HER2+ status was considered as amplification with FISH/CISH (if IHQ++) or NGS, or overexpression (IHQ+++). Data included demographic and clinical characteristics, molecular profile, therapeutic procedures, and efficacy outcomes (EO). Progression-free survival (PFS), overall survival (OS) and time to next therapy (TTNT) were estimated using the Kaplan-Meier method. Results: ERBB2/HER2 status was determined in 448 BTC pt from 31 centers. At diagnosis (dx), 148 pt (33.0%) presented RD and 300 pt AD (67.0%). 128 RD pt experienced tumor relapse. HER2+ was confirmed in 5.4% pt and varied by tumor location: 3.3% in extrahepatic distal and intrahepatic cholangiocarcinoma, 7.3% in extrahepatic hilar and 15.3% in gallbladder carcinoma. Median (m) age at diagnosis in HER2+ pt was 63.8 years; with 75% of women. Treatments were administered in HER2+ and HER2- groups as follows: Surgery in 37.5% vs. 33.0%; locoregional therapy in 4.2% vs 11.6%, neoadjuvant/adjuvant ST in 20.8% vs. 21.7% and ST in AD pt in 100% vs 98.8%. A total of 29 pt (6.5%) received immunotherapy. Metastatic disease occurred in 87.5% of HER2+ vs 77.8% of HER2- pt. Regarding treatments in AD HER2+ pt, most frequent schemes for first and second line were CISGEM (70.6%) and FOLFOX (41.2%) and a total of 29.2% received anti-HER2 therapy. With a m (min, max) follow-up time for the overall population of 16.5 (0.9, 81.2) months (mo), mOS in AD HER2+ pt not treated with anti-HER2 therapies was 13.1 mo (95% CI 9.3-17.0) compared to 15.0 mo (95% CI 13.5-17.3) in HER2- pt (p=0.012) and 32.7 mo (95% CI 20.7-NA) in HER2+ treated pt (p=0.003). EO in first line for HER2+ vs HER2- pt: mPFS 6.6 mo (95% CI 4.5-8.1) vs 6.6 mo (95% CI 5.9-7.7) (p=0.075); mTTNT 7.8 mo (95% CI 6.7-NA) vs 10.0 mo (95% CI 9.2-11.2) (p=0.047); ORR 36.8% vs 27.8% (p = 0.393). Conclusions: This analysis provides insights into the characterization of real-world HER2+ BTC pt showing a significant impact in mOS upon treatment with anti-HER2 therapies.
Martín et al. (2026) studied this question.