Bortezomib in previously treated phosphatase and tension homology‐deficient patients with advanced intrahepatic cholangiocarcinoma: An open‐label, prospective and single‐centre phase II trial

作者：Tianmei Zeng, Tianyi Jiang, Guang Yang, Zhuo Cheng, Cheng Lou, Wei Wei, Chen‐jie Tao, Shouzi Hu, Hui Wang, Hui Wang, Xiao‐wen Cui, Yexiong Tan, Liwei Dong, Hongyang Wang, Hongyang Wang, Zhen-Gang Yuan · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1675 · 被引用次数：5 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Gastric Cancer Management and Outcomes、Histone Deacetylase Inhibitors Research

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarci...