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Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma

Open access
De Jesus-Acosta, Ana, Sugar, Elizabeth A., O’Dwyer, Peter J., Ramanathan, Ramesh K., Von Hoff, Daniel D., Rasheed, Zeshaan, Zheng, Lei, Begum, Asma, Anders, Robert, Maitra, Anirban, McAllister, Florencia, Rajeshkumar, N. V., Yabuuchi, Shinichi, de Wilde, Roeland F., Batukbhai, Bhavina, Sahin, Ismet, Laheru, Daniel A.·2020·British Journal of Cancer

Abstract

Background: The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods: Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results: Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment. Conclusions: Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. Trial registration: ClinicalTrials.gov Identifier: NCT01088815.

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Metadata

Authors
De Jesus-Acosta, A., Sugar, E. A., O’Dwyer, P. J., Ramanathan, R. K., Von Hoff, D. D., Rasheed, Z., Zheng, L., Begum, A., Anders, R., Maitra, A., McAllister, F., Rajeshkumar, N. V., Yabuuchi, S., de Wilde, R. F., Batukbhai, B., Sahin, I., & Laheru, D. A.
Venue
British Journal of Cancer
Published
2019-12-20
Volume
122
Issue
4
Pages
498-505
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
OpenAlex
W2996690712
Cited by
175
References
6
FWCI
7.62
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma. https://app.cochat.ai/papers/10.1038/s41416-019-0683-3
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De Jesus-Acosta, A., Sugar, E. A., O’Dwyer, P. J., Ramanathan, R. K., Von Hoff, D. D., Rasheed, Z., Zheng, L., Begum, A., Anders, R., Maitra, A., McAllister, F., Rajeshkumar, N. V., Yabuuchi, S., de Wilde, R. F., Batukbhai, B., Sahin, I., & Laheru, D. A. (2020). Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma. British Journal of Cancer. https://doi.org/10.1038/s41416-019-0683-3

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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