Role of somatostatin analogs(SSA)in combination with targeted agents(TTA)for neuroendocrine tumors(NETs)A systematic review

Background

SSA are an standard accepted antitumoral treatment for well-differentiated,G-1,2 NETs disregarding site of origin and/or functional status. The effect of the combination of SSA and TTA may be higher than any of its components, as some small retrospective studies have suggested.We aim to determine how that question has been prospectively designed and done in the clinical research field.

Methods

We searched MEDLINE and relevant meetings looking for randomized F2-3 studies and abstracts about testing combinations of SSA(octreoctide, lanreotide, pasireotide) and TTA (sunitinib, everolimus, bevacizumab) Both formal and unplanned combinations were collected in relation to four aspects: Site of tumour (carcinoid (ileal)and non-pancreatic/pancreatic) and functional status(yes/no) For carcinoids the expected appropiate comparison would seem to be SSA vs SSA + TTA("A"),while for pancreatic NETs it should be most probably TTA vs TTA+ SSA("B")An additional search for ongoing trials was also performed.

Results

With respect to comparison "A" only in one study all patients received formal planned SSA-Octreoctide, but it was mainly for functional-symptomatic tumors. No published studies in non-functional non-pancreatic NETs approached the "A" comparison. Ongoing trials in carcinoids tumors are better designed to answer the question but they are only testing lanreotide and pasireotide, not octeotride. No trial have tested Bevacizumab + octreoctide against octreoctide (or other SSA) alone in carcinoid tumors. Otherwise, for comparison "B" in pNETs, two studies analyze everolimus vs everolimus + pasireotide (negative trial), and everolimus + octreoctide( as control arm) plus/minus bevacizumab (with promising results favoring the addition of bevacizumab)

Conclusions

Until now more emphasis have been done in the TTA value of the combination than on the potential antitumor activity and synergy of the SSA. Because of the relative rarity of these tumors it is reasonable to choose, within the hierarchic options, those most pragmatic. However it is the paramount importance to design strategic studies as a proof of concept

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

None

Disclosure

All authors have declared no conflicts of interest.