Tumor Biology

, Volume 36, Issue 2, pp 467–478 | Cite as

Everolimus-based combination for the treatment of advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): biological rationale and critical review of published data

  • Omar Abdel-Rahman
  • Mona Fouad


Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of diseases. Advanced GEP-NENs are considered distinct disease entity with limited treatments. In this review, we will explore the biological rationale and clinical data of everolimus-based combinations for advanced GEP-NENs. PubMed/Medline, the Cochrane Library, and Google Scholar were searched using the terms “GEP-NENs” and “everolimus” and “systemic therapy” and selecting English literature only. Outcomes of interest included progression-free survival and overall survival (PFS and OS), toxicities, and tumor response. A total of 14 potentially relevant trials were initially identified, of which five studies were excluded. Hence, nine trials including 699 patients were included. Median PFS was reported in four out of the nine studies ranging from 14.6 to 16.4 months. The disease control rate was reported in all studies, and it ranged from 75 to 93 %. Frequently reported grade 3/4 toxicities were elevated transaminases, hyperglycemia, and hematologic toxicities. The presence of clinical and statistical heterogeneity of the primary studies precludes reliable evidence-based conclusions. Further well-conducted randomized controlled trials are awaited to better evaluate the treatment of GEP-NENs.


Everolimus Systemic treatment Neuroendocrine neoplasms 


Conflicts of interest


Author’s contributions

OA: Provided the idea and study design and collected the data and wrote the manuscript.

MF: Collected the data and revised the manuscript.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Clinical Oncology, Faculty of MedicineAin Shams UniversityCairoEgypt
  2. 2.Department of Medical Microbiology and Immunology, Faculty of MedicineAin Shams UniversityCairoEgypt

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