Nicola Fazio1, Roberto Buzzoni2, Eric Baudin3, Lorenzo Antonuzzo4, Richard A Hubner5, Harald Lahner6, Wouter W DE Herder7, Markus Raderer8, Alexandre Teulé, Jaume Capdevila9, Steven K Libutti10, Matthew H Kulke11, Manisha Shah12, Debarshi Dey13, Sabine Turri14, Paola Aimone14, Cristian Massacesi15, Chris Verslype16. 1. European Institute of Oncology, Milan, Italy nicola.fazio@ieo.it. 2. IRCCS National Tumor Institute, Milan, Italy. 3. Institut Gustave Roussy, Villejuif, France. 4. Careggi University Hospital, Florence, Italy. 5. The Christie NHS Foundation Trust, Manchester, U.K. 6. University of Duisburg-Essen, Essen, Germany. 7. Erasmus MC, Rotterdam, the Netherlands. 8. University Hospital of Vienna, Vienna, Austria. 9. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 10. Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY, U.S.A. 11. Dana-Farber Cancer Institute, Boston, MA, U.S.A. 12. The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, U.S.A. 13. Novartis Healthcare Private Limited, Hyderabad, India. 14. Novartis Pharma AG, Basel, Switzerland. 15. Novartis Oncology, Paris, France. 16. University Hospitals Leuven, Leuven, Belgium.
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. Copyright
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. Copyright
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