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Clinical Trial
. 2016 Feb;36(2):713-9.

A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours

Nicola Fazio  1 , Roberto Buzzoni  2 , Eric Baudin  3 , Lorenzo Antonuzzo  4 , Richard A Hubner  5 , Harald Lahner  6 , Wouter W DE Herder  7 , Markus Raderer  8 , Alexandre Teulé, Jaume Capdevila  9 , Steven K Libutti  10 , Matthew H Kulke  11 , Manisha Shah  12 , Debarshi Dey  13 , Sabine Turri  14 , Paola Aimone  14 , Cristian Massacesi  15 , Chris Verslype  16
Affiliations
Clinical Trial

A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours

Nicola Fazio et al. Anticancer Res. 2016 Feb.

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 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.

Keywords: BEZ235; PI3K; everolimus; mTOR; pNETs.

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Conflict of interest statement

CV has received honoraria from Bayer, Novartis, and Ipsen. EB has received funding to attend ASCO 2013 and ESMO 2015. LA has received honoraria from Roche, Novartis, Ipsen, Merck, and Eli Lilly. MS has received research funding from Novartis. NF has received honoraria from Ipsen and Novartis, and research funding from Novartis. RB reports research funding from Novartis. WWdH has received research funding from Ipsen and Novartis. DD, ST, and PA are employees of Novartis. CM is an employee and shareholder of Novartis. All remaining authors (AT, HL, JC, MHK, MR, RAH, SKL) have declared no conflicts of interest. The study was funded by Novartis Pharmaceuticals Corporation and designed in conjunction with the steering committee. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

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