WITHDRAWN: Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: an open-label, prospective, phase II trial

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic options. To explore phosphatase and tension homology deleted on chromosome ten (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: Between July 1, 2017, and June 30, 2021, a total of 130 patients with advanced ICC were screened by PTEN immunohistochemical staining and 16 patients were enrolled. Patients with PTEN deficiency who had progressed after gemcitabine combined cisplatin received single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Results: The median time of follow up was 4.63 months (95% CI: 0.7~17.2 months). Among the 16 enrolled patients, 13 of them had completed treatment with bortezomib at least 2 cycles and been evaluated. The ORR was 23% (3/13) and disease control rate was 54% (7/13). The median progress-free survival (mPFS) was 2.95 months (95% CI: 2.1~5.1 months) and the median overall survival (mOS) was 7.2 (95% CI: 0.7~21.6 months) 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 score of 0 were more likely to benefit from bortezomib than those with staining score > 0. Conclusions: Bortezomib yielded encouraging objective response and a favorable overall survival as a second-line therapy in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising treatment option in selected ICC patients with PTEN deficiency. Trial Registration: ClinicalTrials.gov (NCT03345303).