التفاصيل البيبلوغرافية
| العنوان: |
Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor‐Naïve Advanced Pancreatic Neuroendocrine Tumors |
| المؤلفون: |
Salazar, Ramon, Garcia‐Carbonero, Rocio, Libutti, Steven K, Hendifar, Andrew E, Custodio, Ana, Guimbaud, Rosine, Lombard‐Bohas, Catherine, Ricci, Sergio, Klümpen, Heinz‐Josef, Capdevila, Jaume, Reed, Nicholas, Walenkamp, Annemiek, Grande, Enrique, Safina, Sufiya, Meyer, Tim, Kong, Oliver, Salomon, Herve, Tavorath, Ranjana, Yao, James C |
| المصدر: |
The Oncologist, vol 23, iss 7 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2018 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Orphan Drug, Rare Diseases, Cancer, Clinical Trials and Supportive Activities, Digestive Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Antineoplastic Agents, Everolimus, Female, Humans, Imidazoles, Male, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Middle Aged, Neuroendocrine Tumors, Pancreatic Neoplasms, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Progression-Free Survival, Quinolines, TOR Serine-Threonine Kinases, Oncology & Carcinogenesis |
| جغرافية الموضوع: |
766 - e90 |
| الوصف: |
Lessons learnedTreatment 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.BackgroundThis 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.MethodsPatients 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.ResultsEnrollment 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%).ConclusionBEZ235 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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt0kx1d252; https://escholarship.org/uc/item/0kx1d252Test |
| الإتاحة: |
https://escholarship.org/uc/item/0kx1d252Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.ACF7F187 |
| قاعدة البيانات: |
BASE |
