Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

ABSTRACT

Introduction: Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs.

Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines.

Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.

KEYWORDS:

• Neuroendocrine tumor (NET)
• everolimus
• mammalian target of rapamycin (mTOR) inhibitor
• RADIANT trials

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript was partially supported by intramural funds from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (Grant No. DK053200-26).