53P FGFR2 fusion and/or rearrangement profiling in Chinese patients with intrahepatic cholangiocarcinoma

Xw, Huang; Shi, G-M.; Zhang, T.; Bao, L-Q.; Tf, Wen; Zhang, B.; Tang, Peng; Zhao, He; Kuang, Ming; Wl, Wang; Jh, Ran; Yb, Liu; Gong, Weijuan; Mou, H-B.; Luo, Yuzhong; Wang, Y.; Sun, Hui; Fan, Junwei; Lx, Liu; Dai, Menghua

doi:10.1016/j.annonc.2021.08.332

Cited by 3 publications

(3 citation statements)

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“…To date, no drugs and regimens succeeded in prolonging the PFS or OS to a signi cant extent after GC except for FGFR inhibitors. However, FGFR inhibitors could only bene t less than 15% of ICC patients [12],which is even lower in the Chinese population (6.14%) [13], whereas PTEN de ciency occurred in about 30% of the ICC patients in our study. Here, we reported a 23% objective response, which was only inferior to prior reports on FGFR inhibitors [11,14], yet indicated signi cant improvement to other secondline regimens, such as FOLFOX (5%) [2], regorafenib (11%) [15] and lenvatinib plus pembrolizumab (10%) [16].…”

Section: Discussioncontrasting

confidence: 63%

WITHDRAWN: Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: an open-label, prospective, phase II trial

Zeng

Jiang²,

Yang

et al. 2023

Preprint

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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).

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Section: Discussioncontrasting

confidence: 63%

WITHDRAWN: Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: an open-label, prospective, phase II trial

Zeng

Jiang²,

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…To date, no drugs and regimens other than FGFR inhibitors have succeeded in significantly prolonging PFS or OS following GC treatment. However, FGFR inhibitors only benefit less than 15% of ICC patients, 16 with an even lower rate (6.14%) in the Chinese population 17 . In contrast, approximately 30% of ICC patients in our study exhibited PTEN deficiency.…”

Section: Discussioncontrasting

confidence: 59%

“…However, FGFR inhibitors only benefit less than 15% of ICC patients, 16 with an even lower rate (6.14%) in the Chinese population. 17 In contrast, approximately 30% of ICC patients in our study exhibited PTEN deficiency. Notably, the ORR in our study was 23.08% in the PP cohort, which was only inferior to previous reports on FGFR inhibitors, 15 , 18 yet indicated a significant improvement compared to other second‐line regimens, such as FOLFOX (5%), 3 regorafenib (11%), 19 and lenvatinib plus pembrolizumab (10%).…”

Section: Discussioncontrasting

confidence: 56%

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

Zeng,

Jiang,

Yang

et al. 2024

Clinical & Translational Med

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IntroductionIntrahepatic 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.MethodsA total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single‐agent bortezomib 1.3 mg/m2 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.ResultsThe 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.ConclusionsBortezomib 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 cholangiocarcinoma (ICC). This investigator‐initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent‐to‐treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

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

2023

Preprint

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53P FGFR2 fusion and/or rearrangement profiling in Chinese patients with intrahepatic cholangiocarcinoma

Cited by 3 publications

References 0 publications

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

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

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

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

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