Real-world outcomes of trastuzumab plus chemotherapy in HER2-positive biliary tract cancers from a high-incidence region.

Abstract

e16234 Background: Biliary tract cancers (BTCs), particularly gallbladder carcinoma (GBC), are aggressive malignancies with a disproportionately high burden in Northern India. HER2 overexpression or amplification is a clinically actionable alteration in a subset of BTCs. However, prospective randomized data for HER2-directed therapy in BTC are limited. We evaluated the real-world effectiveness of trastuzumab combined with chemotherapy in patients with HER2-positive BTC. Methods: We conducted a retrospective cohort study of 67 consecutive patients with HER2-positive BTC (IHC 3+ or IHC 2+ with amplification) treated between 2019 and 2024. Clinical and pathological characteristics were summarized descriptively. Patients received standard platinum- or fluoropyrimidine-based chemotherapy with or without trastuzumab. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan–Meier method and compared using the log-rank test. Results: The median age was 51 years (range, 28–74), with 69% female patients. Gallbladder carcinoma comprised 97% of cases, and 88% had HER2 IHC 3+ expression. Metastatic disease at presentation was present in 75% of patients. Trastuzumab was administered to 35 patients (52%), including 24 (69%) in the first-line setting. At a median follow-up of 12.6 months, median PFS was 6.0 months (95% CI, 4.9–6.4) in the trastuzumab group compared with 1.8 months (95% CI, 1.4-3.8) in the non-trastuzumab group (p < 0.001), representing an approximately 3-fold improvement. Median OS was 8.5 months (95% CI, 6.4-9.4) with trastuzumab versus 2.1 months (95% CI, 1.5-2.7) without trastuzumab (p < 0.001). The 6-month OS rate was 83.9% in the trastuzumab cohort compared with 16.6% in the control cohort. Conclusions: In this real-world cohort from a high-incidence region, the addition of trastuzumab to chemotherapy resulted in a clinically and statistically significant improvement in PFS and OS in patients with HER2-positive BTC. These data support routine HER2 testing and integration of HER2-targeted therapy into standard treatment algorithms for this molecularly defined subgroup.