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.

BEZ235, Everolimus, MTOR, PI3K, PNETs
Anticancer Research
Erasmus MC: University Medical Center Rotterdam

Fazio, N, Buzzoni, R, Baudin, E, Antonuzzo, L, Hubner, R.A, Lahner, H, … Verslype, C. (2016). A phase II study of BEZ235 in patients with everolimusresistant, advanced pancreatic neuroendocrine tumours. Anticancer Research, 36(2), 713–720. Retrieved from

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