Feasibility of HER2-Targeted Therapy in Advanced Biliary Tract Cancer: A Prospective Pilot Study of Trastuzumab Biosimilar in Combination with Gemcitabine Plus Cisplatin.

The prognosis of advanced biliary tract cancer (BTC) is poor with the standard gemcitabine and cisplatin (GemCis) regimen. Given that the rates of human epidermal growth factor receptor 2 (HER2) positivity in BTC reaches around 15%, HER2-targeted therapy needs further investigation. This study aims to evaluate the preliminary efficacy/safety of first-line trastuzumab-pkrb plus GemCis in patients with advanced BTC. Patients with unresectable/metastatic HER2-positive BTC received trastuzumab-pkrb (on day 1 of each cycle, 8 mg/kg for the first cycle and 6 mg/kg for subsequent cycles), gemcitabine (1000 mg/m on day 1 and 8) and cisplatin (25 mg/m on day 1 and 8) every 3 weeks. Of the 41 patients screened, 7 had HER2-positive tumours and 4 were enrolled. The median age was 72.5 years (one male). Primary tumour locations included extrahepatic (N = 2) and intrahepatic (N = 1) bile ducts, and gallbladder (N = 1). Best overall response was a partial response in two patients and stable disease in two patients. Median progression-free survival (PFS) was 6.1 months and median overall survival (OS) was not reached. The most common grade 3 adverse event was neutropenia (75%), but febrile neutropenia did not occur. No patient discontinued treatment due to adverse events. Trastuzumab-pkrb with GemCis showed promising preliminary feasibility in patients with HER2-positive advanced BTC.