TY - JOUR T1 - A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours JF - Anticancer Research JO - Anticancer Res SP - 713 LP - 719 VL - 36 IS - 2 AU - NICOLA FAZIO AU - ROBERTO BUZZONI AU - ERIC BAUDIN AU - LORENZO ANTONUZZO AU - RICHARD A. HUBNER AU - HARALD LAHNER AU - WOUTER W. DE HERDER AU - MARKUS RADERER AU - ALEXANDRE TEULÉ AU - JAUME CAPDEVILA AU - STEVEN K. LIBUTTI AU - MATTHEW H. KULKE AU - MANISHA SHAH AU - DEBARSHI DEY AU - SABINE TURRI AU - PAOLA AIMONE AU - CRISTIAN MASSACESI AU - CHRIS VERSLYPE Y1 - 2016/02/01 UR - http://ar.iiarjournals.org/content/36/2/713.abstract N2 - Background: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant 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 progression-free 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. ER -