Target therapies plus somatostatin analogues in NETs: a network meta-analysis

in Endocrine-Related Cancer
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  • 1 S Pusceddu, Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, 20133, Italy
  • 2 A Facciorusso, Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
  • 3 L Giacomelli, Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genova, Italy
  • 4 N Prinzi, Department of Medical Oncology , Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
  • 5 F Corti, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy
  • 6 M Niger, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 7 M Milione, 1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
  • 8 J Coppa, Liver Surgery, Transplantation and Gastroenterology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
  • 9 T Cascella, Radiology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 10 I Pulice, Clinical Trial Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 11 L Biamonte, Clinical Trial Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 12 S Papa, NA, Polistudium srl, Milano, Italy
  • 13 M Di Bartolomeo, Department of Medical Oncology , Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
  • 14 A Shah, NA, Polistudium srl, Milano, Italy
  • 15 R Sacco, Gastroenterology Unit, Department of Surgical and Medical Sciences, University of Foggia, Foggia, Italy
  • 16 F de Braud, Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy

Correspondence: Sara Pusceddu, Email: sara.pusceddu@istitutotumori.mi.it
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Although combination therapy is not recommended in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs), this strategy is widely used in clinical practice. This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP advanced NETs, either alone or in combination, comparing the efficacy of different single or combined treatment strategies in terms of progression-free survival (PFS). Interventions were grouped as analogues, everolimus, everolimus plus SSAs, sunitinib and placebo. In a secondary analysis, we also assessed the efficacy of individual specific pharmacological treatments versus placebo or each other. From 83 studies identified, 8 randomized controlled trials were selected, with a total of 1849 patients with either functioning or non-functioning NETs. The analysis confirmed the superiority of all treatments over placebo (HR ranging from 0.34, 95% CI: 0.24–0.37 with the combination of everolimus plus SSAs to 0.42, 0.31–0.57 with the analogues; moderate quality of evidence). On ranking analysis, the combination of everolimus plus SSA (P score=0.86) and then everolimus alone (P score=0.65) ranked highest in increasing PFS. On comparative evaluation of different interventions, pasireotide (P score=0.96) and everolimus+octreotide (P score=0.82) ranked as the best pharmacological treatment options. Our findings support the use of combination therapy in the treatment of functioning and non-functioning GEP NETs. The role of pasireotide should be explored in selected subgroups of patients. Last, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.