Bortezomib plus gemcitabine-cisplatin versus gemcitabine-cisplatin as first-line treatment for advanced biliary tract cancers: A randomized phase II clinical trial with exploratory analysis of PTEN status.

作者：Hui Wang, Xinru Fan, Tianmei Zeng, Lufan Xie, Tianyi Jiang, Q Wang, Tuan Zhao, Song Zheng, Hai‐Hua Zhou, X Xu, Heping Hu, Hongyang Wang, Zhengang Yuan, Liwei Dong · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.4112 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Tannin, Tannase and Anticancer Activities、Gastric Cancer Management and Outcomes

4112 Background: Biliary tract cancers (BTCs) are aggressive malignancies with limited treatment and poor prognosis, including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (perihilar and distal), gallbladder cancer and ampullary cancer. Our previous research indicated that bortezomib is a promising treatment option as proteasome inhibitor in PTEN-loss iCCA patients (Clin Transl Med. 2024 May;14(5): e1675). In this randomized phase II clinical trial, we expanded the indication to BTCs and explored clinical benefit and safety of bortezomib plus gemcitabine-cisplatin (GPB) compared with gemcitabine-cisplatin (G based) as first line treatment for advanced BTCs and further evaluated the potential predictive value of PTEN status. Methods: Between September 1, 2020, and December 31,2023, a total of 105 patients were screened. 59 patients were enrolled. The 59 patients were randomly assigned to either GPB group (n = 32) or G based group (n=27). PTEN status was not known at the time of randomization. PTEN immunohistochemical staining was subsequently performed in all patients identifying 18 patients (30.5%) with PTEN loss (PTEN=0) and 41 patients (69.5%) with PTEN expression (PTEN=1). The GPB regimen consisted of gemcitabine 1000 mg/m 2 day 1,8, cisplatin 75 mg/m 2 day 1, 8, plus bortezomib 1.3 mg/m 2 day 1, 4, 8, and 11 of a 21-day cycle. The G based group received gemcitabine based regimens including G-cisplatin (GP), G-Oxaliplatin (GMOX) or G-S-1 (GS). Th...