Sequential treatment in disseminated well- and intermediate-differentiated pancreatic neuroendocrine tumors: Common sense or low rationale?

Fortunately, the landscape of the systemic treatment for grade 1 and 2 pancreatic neuroendocrine tumors has changed in the last decade with at least four different alternatives approved in the field. Chemotherapy, somatostatin analogues, sunitinib and everolimus remind valid options according to the most referenced international guidelines. However, and although this is something done in the routine practice, there is a lack of evidence for the use of any of these strategies after failure to the others. Moreover, further sequential alternatives in third or fourth line have never been tested prospectively. The need for a better understanding of the rationale to sequence different systemic options is even greater in non-pancreatic neuroendocrine tumors since available therapies are scarce. Sequential strategies in other solid tumors have led to a clear improvement in overall survival. This is also believed to occur in neuroendocrine tumors but no clear data on it has been delivered yet. We postulate that the different mode of action of the systemic options available for the treatment of neuroendocrine tumors may avoid the complete resistance of one option after the other and that sequential use of these agents will be translated into a longer overall survival of patients. Prospective and randomized trials that seek for the activity of drugs after failure to another systemic alternatives are highly needed in this field of neuroendocrine tumors.