Abstract
Background: The treatment options for GEP-NENs include various drugs and are based on grading, morphology, and location of the primary.
Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs.
Methods: A scientific literature search from 2015 to January 2020 was performed using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included.
Results: Several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays, the current knowledge in this field is mainly based on phase I-II studies. Immunotherapy showed limited antitumor activity, but a higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment.
Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays, we see many gaps in this field. We must balance therapeutic possibilities offered by precision oncology with an understanding of the limitations of the application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to a candidate for immunotherapy in terms of disease characteristics and previous treatments and how to select them with accurate biomarkers.
Keywords: Gastroenteropancreatic, neuroendocrine, tumors, checkpoint inhibitors, immunotherapy, PD-L1.
Graphical Abstract
[http://dx.doi.org/10.1111/his.13975] [PMID: 31433515]
[http://dx.doi.org/10.1097/01.sla.0000129342.67174.67] [PMID: 15213627]
[http://dx.doi.org/10.1001/jamaoncol.2017.0589] [PMID: 28448665]
[http://dx.doi.org/10.1002/cncr.31124] [PMID: 29211313]
[http://dx.doi.org/10.1200/JCO.2009.22.8510] [PMID: 19704057]
[http://dx.doi.org/10.1056/NEJMoa1316158] [PMID: 25014687]
[http://dx.doi.org/10.1056/NEJMoa1009290] [PMID: 21306238]
[http://dx.doi.org/10.1056/NEJMoa1003825] [PMID: 21306237]
[http://dx.doi.org/10.1056/NEJMoa1607427] [PMID: 28076709]
[http://dx.doi.org/10.1159/000443612] [PMID: 26731483]
[http://dx.doi.org/10.1007/s12020-020-02475-2] [PMID: 33052555]
[http://dx.doi.org/10.1002/cncr.25425] [PMID: 20824724]
[http://dx.doi.org/10.1007/s12020-020-02421-2] [PMID: 32700133]
[http://dx.doi.org/10.1159/000444087] [PMID: 26789262]
[http://dx.doi.org/10.1159/000497336] [PMID: 30703770]
[http://dx.doi.org/10.1159/000511905] [PMID: 33002892]
[http://dx.doi.org/10.1002/cncr.29099] [PMID: 25312765]
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[http://dx.doi.org/10.1016/S1470-2045(18)30700-9] [PMID: 30361170]
[http://dx.doi.org/10.1016/S1470-2045(17)30616-2] [PMID: 28967485]
[http://dx.doi.org/10.1200/JCO.19.01213] [PMID: 32552471]
[http://dx.doi.org/10.1056/NEJMoa1606774] [PMID: 27718847]
[http://dx.doi.org/10.1002/bjs.4149] [PMID: 12808615]
[http://dx.doi.org/10.1016/S0016-5085(00)70143-0] [PMID: 10734025]
[http://dx.doi.org/10.1111/j.1477-2574.2010.00231.x] [PMID: 21083792]
[http://dx.doi.org/10.1080/02841860802438495] [PMID: 18855160]
[http://dx.doi.org/10.1159/000334612] [PMID: 22248635]
[http://dx.doi.org/10.1530/ERC-18-0494] [PMID: 30608901]
[http://dx.doi.org/10.1530/ERC-18-0189] [PMID: 30400003]
[http://dx.doi.org/10.1097/MPA.0000000000001150] [PMID: 30153220]
[http://dx.doi.org/10.3892/ol.2017.7569] [PMID: 29434915]
[http://dx.doi.org/10.1038/cddis.2017.401] [PMID: 28837143]
[http://dx.doi.org/10.7150/jca.13711] [PMID: 26958083]
[http://dx.doi.org/10.18632/oncotarget.24464] [PMID: 29599916]
[http://dx.doi.org/10.5858/arpa.2010-0560-OA] [PMID: 22129180]
[http://dx.doi.org/10.1530/ERC-14-0410] [PMID: 25465415]
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0735] [PMID: 29523759]
[http://dx.doi.org/10.1093/annonc/mdx368]
[http://dx.doi.org/10.5858/arpa.2015-0544-OA] [PMID: 27788043]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3014] [PMID: 31980466]
[http://dx.doi.org/10.1093/annonc/mdy293.001]
[http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.4103]
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3356] [PMID: 31969335]
[http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.2570]
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.TPS4146]
[http://dx.doi.org/10.1200/JCO.2020.38.4_suppl.619]
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[http://dx.doi.org/10.1200/JCO.2018.78.2276] [PMID: 30557521]
[http://dx.doi.org/10.1084/jem.20100643] [PMID: 20819927]
[http://dx.doi.org/10.1038/ncomms10501] [PMID: 26883990]
[http://dx.doi.org/10.1126/science.aar3593]
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.6009]
[http://dx.doi.org/10.1172/JCI91190] [PMID: 28650338]
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.4013]
[http://dx.doi.org/10.1056/NEJMoa1503093] [PMID: 25891173]
[http://dx.doi.org/10.1016/S1470-2045(20)30445-9] [PMID: 32919526]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0883] [PMID: 16166452]
[http://dx.doi.org/10.1007/s00432-003-0492-0] [PMID: 14564514]
[http://dx.doi.org/10.1371/journal.pone.0032542] [PMID: 22396773]
[http://dx.doi.org/10.1016/j.ctrv.2012.06.009] [PMID: 22819619]
[http://dx.doi.org/10.1016/S1470-2045(16)30098-5] [PMID: 27269741]
[http://dx.doi.org/10.1056/NEJMoa1809064] [PMID: 30280641]
[http://dx.doi.org/10.1038/nature24673] [PMID: 29186113]
[http://dx.doi.org/10.1002/cac2.12114] [PMID: 33230973]