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.

Asphericity of Somatostatin Receptor Expression in Neuroendocrine Tumors: An Innovative Predictor of Outcome in Everolimus Treatment?

“…While these two studies may only be compared very cautiously, the combined results might indicate that patients with ASP values between 5.5% and 12.9% might be candidates for treatment with mTor-inhibitors rather than PRRT. According to the North American Neuroendocrine Tumor Society (NANETS) guidelines for the treatment of advanced midgut NETs from 2017 [25], everolimus is also recommended as first-line therapy in patients who are no candidates for SSAs (e.g., weak or absent SSR expression). It is important to notice that the definition "weak" is a challenging definition for interdisciplinary consensus.…”

A study on the protective mechanism of mTOR inhibitor Everolimus on brain injury after epilepsy

“…In previous studies, Everolimus indirectly affected neuronal excitability by modulating specific ion channels such as potassium channels or proteins [33]. Currently, clinical use of Everolimus is primarily for anti-rejection of organ transplantation, autoimmune diseases and anti-tumor treatment [34][35][36]. Research on epilepsy is still very limited.…”

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

“…On the other hand, a high tolerability is also related to low rates of drug interruption and discontinuation and consequently is likely to induce a better effectiveness. In this setting, whereas SSA are widely accepted as firstline treatment, because of their positive benefit/risk ratio, no data are available to establish the best choice as second-line treatment [22,23]. This is the first study with the purpose of trying to answer this unmet need, by analyzing and comparing the main therapeutic sequences in a large retrospective series of G1−G2 NET.…”