Abstract 5954: Real-world (RW) second-line (2L) treatment (tx) patterns and clinical outcomes in patients (pts) with HER2-overexpressing biliary tract cancer (BTC)
Authors: Richard Kim, Xiaozhou Fan, Javier Sabater, Wayne Su, Kathleen Hurwitz, Kayla Hendrickson, Catherine Wiener, Phillip Garfin, Joan Zape, Mark A. Ozog, John Bridgewater, Juan W. Valle, Farshid Dayyani
Journal: Cancer Research (2025)

Abstract Background: HER2 has emerged as a target for precision therapies in BTC. We describe the RW tx patterns and overall survival (OS) of pts with advanced HER2-overexpressing BTC treated in the 2L. Methods: This retrospective observational study used the Flatiron Health Electronic Health Record-derived, deidentified database (01/2011 to 12/2023). Pts with HER2-overexpressing (IHC 3+) BTC who received 2L tx ≥6 months (mo) of potential follow-up time were included in the OS analysis. Follow-up began at initiation of 2L tx (index) to the earliest of last recorded activity, death, or end of data. Concordance between HER2 overexpression and amplification was assessed in all pts, regardless of HER2 status, with available testing results from IHC, (F)ISH, and NGS . Results: Among 29, 817 pts with BTC, 36 pts were included in the OS analysis; median age was 67 (range: 49-83) years. 47% of pts received 2L HER2-targeted therapy including pertuzumab + trastuzumab (HP; n=7), trastuzumab + chemotherapy (n=6), trastuzumab deruxtecan (n=2), HP + chemo (n=1), and HP + anti-PD-(L)1 (n=1). Non-HER2-targeted therapies included chemo only (n =14), chemo + anti-PD-(L)1 (n=3), and non-HER2 tyrosine kinase inhibitors ± bevacizumab (n=2). Diabetes and chronic pulmonary disease were more frequent in pts who received non-HER2-targeted therapy (Table). Median OS was 9.9 (95%CI 5.5-29.4) mo overall (HER2-targeted : 13.2 mo; non-HER2-targeted : 8.5 mo; and chemo only: 5.6 mo). Median OS was 8.7 mo in pts with ECOG 0 or 1 (n=21). Among the 80 pts in the concordance analysis, 79% and 90% of pts with HER2 overexpression had HER2 amplification as detected by NGS and (F)ISH, respectively. Conclusions: The OS of pts with HER2 overexpression in the RW who received chemo only was consistent with previously reported OS for chemo only in 2L BTC regardless of HER2 status. In pts with HER2-overexpressing BTC, HER2-targeted therapy showed a numerical improvement in OS vs. chemo only. OverallN=36 HER2-targetedn=17 Non-HER2-targetedn=19 chemo only n=14 ECOG 0-1n=21 Median age (years) 67 66 68 68 66 Female (%) 67 65 68 71 67 ECOG 0-1 (%) 75 69 80 83 100 Anatomical subtype (%) GBC 61 65 58 71 62 iCCA 31 23 37 29 33 eCCA 8 12 5 0 5 Diabetes (%) 50 24 74 64 38 Chronic pulmonary disease (%) 36 29 42 43 33 Stage III-IV at initial dx (%) 78 69 86 80 73 Index year 2017-2023 (%) 92 94 90 93 95 Citation Format: Richard Kim, Xiaozhou Fan, Javier Sabater, Wayne Su, Kathleen Hurwitz, Kayla Hendrickson, Catherine Wiener, Phillip Garfin, Joan Zape, Mark A. Ozog, John Bridgewater, Juan W. Valle, Farshid Dayyani. Real-world (RW) second-line (2L) treatment (tx) patterns and clinical outcomes in patients (pts) with HER2-overexpressing biliary tract cancer (BTC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5954.