Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms

In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multi-target tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by regulatory agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in depth review on the studies published on the following MTKIs in neuroendocrine tumours: axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on clinical trial registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastro-entero-pancreatic and lung NENs identifies in vitro and in vivo studies which demonstrate anti-tumour activity of diverse MTKIs on neuroendocrine cells and tumours. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II, and III clinical trials are ongoing and will include, overall, a staggering 1667 patients. This fervid activity underlines the increasing interest of the scientific community in the use of emerging MTKIs in NEN treatment.