A phase II study of BEZ235 in patients with everolimusresistant, advanced pancreatic neuroendocrine tumours

Nicola Fazio, Roberto Buzzoni, E. Baudin, Lorenzo Antonuzzo, Richard A. Hubner, Harald Lahner, Wouter De Herder, Markus Raderer, A. Teulé, Jaume Capdevila, Steven K. Libutti, Matthew H. Kulke, Manisha Shah, Debarshi Dey, Sabine Turri, Paola Aimone, Cristian Massacesi, Chris Verslype

Research output: Contribution to journalArticle

Abstract

Background: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimusresistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). Patients and Methods: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progressionfree survival (PFS) rate of =60% in stage 1. Results: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). Conclusion: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2. Pancreatic neuroendocrine tumours (pNETs) are rare malignancies, representing

Original languageEnglish
Pages (from-to)713-720
Number of pages8
JournalAnticancer Research
Volume36
Issue number2
Publication statusPublished - Feb 1 2016

Keywords

  • BEZ235
  • Everolimus
  • MTOR
  • PI3K
  • PNETs

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Fazio, N., Buzzoni, R., Baudin, E., Antonuzzo, L., Hubner, R. A., Lahner, H., De Herder, W., Raderer, M., Teulé, A., Capdevila, J., Libutti, S. K., Kulke, M. H., Shah, M., Dey, D., Turri, S., Aimone, P., Massacesi, C., & Verslype, C. (2016). A phase II study of BEZ235 in patients with everolimusresistant, advanced pancreatic neuroendocrine tumours. Anticancer Research, 36(2), 713-720.