Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors
Year: 2017
Type: article
Study design: Clinical Trial
Abstract: LESSONS LEARNED: Treatment with BEZ235 has not been shown to demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.The hypothesis of dual targeting of the phosphatidylinositol 3-kinase and mammalian target of rapamycin pathways in patients with advanced pancreatic neuroendocrine tumors may warrant further study using other agents. BACKGROUND: This phase II study investigated whether targeting the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway via PI3K, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) inhibition using BEZ235 may be more effective than mTORC1 inhibition with everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET) who are naïve to mTOR inhibitor therapy. METHODS: Patients with advanced pNET were randomized (1:1) to oral BEZ235 400 mg twice daily or oral everolimus 10 mg once daily on a continuous dosing schedule. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, overall response rate (ORR), overall survival (OS), and time to treatment failure. RESULTS: Enrollment in this study was terminated early (62 enrolled of the 140 planned). The median PFS was 8.2 months (95% confidence interval [CI]: 5.3 to not evaluable [NE]) with BEZ235 versus 10.8 months (95% CI: 8.1-NE) with everolimus (hazard ratio 1.53; 95% CI: 0.72-3.25). The most commonly reported all-grade adverse events (>50% of patients regardless of study treatment relationship) with BEZ235 were diarrhea (90.3%), stomatitis (74.2%), and nausea (54.8%). CONCLUSION: BEZ235 treatment in mTOR inhibitor-naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile.
Source: The Oncologist
Authors: Ramon Salazar, Rocio Garcia-Carbonero, Steven K. Libutti, Andrew E. Hendifar, Ana Custodio, Rosine Guimbaud, Catherine Lombard-Bohas, Sergio Ricci, Heinz-Josef Klümpen, Jaume Capdevila, Nicholas Reed, Annemiek Walenkamp, Enrique Grande, Sufiya Safina, Tim Meyer, Oliver Kong, Herve Salomon, Ranjana Tavorath, James C. Yao
Institutions: Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universitat de Barcelona, Hospital Universitario 12 De Octubre, Albert Einstein College of Medicine, Cedars-Sinai Medical Center, Hospital Universitario La Paz, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Hôpital Lyon Sud, University of Pisa, Amsterdam UMC Location University of Amsterdam, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Beatson West of Scotland Cancer Centre, University Medical Center Groningen, University of Groningen, Hospital Universitario Ramón y Cajal, Kazan State Medical University, The Royal Free Hospital, Novartis (United States), Novartis (France), The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2771377667