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

Published on Jul 1, 2021in Endocrine-related Cancer5.678
· DOI :10.1530/ERC-20-0492
Sara Pusceddu18
Estimated H-index: 18
Antonio Facciorusso21
Estimated H-index: 21
(University of Foggia)
+ 13 AuthorsFilipppo de Braud
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.
#1Barbara Kiesewetter (Medical University of Vienna)H-Index: 18
#2Markus Raderer (Medical University of Vienna)H-Index: 79
Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyros...
#1Marianne PavelH-Index: 54
#2Kjell Öberg (Uppsala University)H-Index: 117
Last. Alfredo Berruti (University of Brescia)H-Index: 67
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Abstract There is a recent update in WHO classification of pancreatic neuroendocrine neoplasms (PanNENs). Our aims are to analyse the latest management for patients with PanNENs according to the current classification of these neoplasms. The primary treatment is curative surgery and the surgical procedures depends on size, location, and histopathology of the tumour. Even if tumour has metastases, debulking surgery or resection of the primary lesion could improve the prognosis of these patients. ...
#1Natalie PrinziH-Index: 14
#2Alessandra RaimondiH-Index: 12
Last. Sara PuscedduH-Index: 18
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: Aim: Data from 69 well-differentiated gastroenteropancreatic neuroendocrine tumors treated with peptide receptor radionucleotide therapy + somatostatin analogs (SSAs) after SSA treatment failure were evaluated. Methods: We identified two groups: S1 - patients who kept the same SSA treatment beyond progression; S2 - patients who switched the SSA with another SSA after progression. Results: Median progression-free survival was 53 and 127 months in S1 and S2, respectively (p = 0.001; hazard ratio...
#1Anna Kathrin Stueven (Charité)H-Index: 2
#2Antonin Kayser (Charité)H-Index: 2
Last. Henning Jann (Charité)H-Index: 12
view all 9 authors...
In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has...
#1Jaume Capdevila (Hebron University)H-Index: 34
#2Alexandre TeuléH-Index: 3
Last. Ramon SalazarH-Index: 41
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BACKGROUND: Antitumor activity of the combination of somatostatin analogues (SSAs) and the mammalian target of rapamycin (mTOR) inhibitor everolimus in patients with neuroendocrine tumors (NETs) has been reported but not confirmed in prospective trials. MATERIALS AND METHODS: This prospective, multicenter, single-arm phase II EVERLAR study evaluated everolimus 10 mg/day and the SSA octreotide 30 mg every 28 days in patients with advanced nonfunctioning well-differentiated gastrointestinal NETs (...
Mixed adenoneuroendocrine carcinomas (MANECs) are composed of a poorly differentiated neuroendocrine carcinoma (NEC) and a non-neuroendocrine (non-NEC) neoplastic epithelial component, each representing at least 30% of the tumor. At present, prognostic factors for MANECs remain largely unexplored. We investigated the clinical-pathologic features of a large multicenter series of digestive system MANECs. Surgical specimens of 200 MANEC candidates were centrally reviewed; diagnosis was confirmed in...
#1Bryan OronskyH-Index: 25
#2Patrick C. Ma (WVU: West Virginia University)H-Index: 20
Last. Corey A. Carter (Walter Reed National Military Medical Center)H-Index: 25
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Abstract This review covers the diverse topic of neuroendocrine neoplasms (NENs), a relatively rare and heterogeneous tumor type, comprising ~2% of all malignancies, with a prevalence of 1 For functional purposes, NENs are divided into two groups on the basis of clinical behavior, histology, and proliferation rate: well differentiated (low grade to intermediate grade) neuroendocrine tumors and poorly differentiated (high grade) neuroendocrine carcinoma (Bosman et al., 2010) 2 ; this histological...
#1Sara PuscedduH-Index: 18
#2Filippo de BraudH-Index: 70
Last. Roberto BuzzoniH-Index: 32
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// Sara Pusceddu 1,2 , Filippo De Braud 1,2 , Giuseppe Lo Russo 1,2 , Laura Concas 1,2 , Daniela Femia 1,2 , Claudio Vernieri 1,2 , Alice Indini 1,2 , Barbara Formisano 1,2 and Roberto Buzzoni 1,2 1 Medical Oncology Department, ENETs Center of Excellence, Milan, Italy 2 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Correspondence to: Sara Pusceddu, email: // Keywords : everolimus, neuroendocrine tumors Received : December 14, 2015 Accepted : March 10, 2016 Published : April 05, 20...
#1Milo A. Puhan (Prevention Institute)H-Index: 79
#2Holger J. Schünemann (McMaster University)H-Index: 158
Last. Gordon H. Guyatt (McMaster University)H-Index: 267
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Network meta-analysis (NMA), combining direct and indirect comparisons, is increasingly being used to examine the comparative effectiveness of medical interventions. Minimal guidance exists on how to rate the quality of evidence supporting treatment effect estimates obtained from NMA. We present a four-step approach to rate the quality of evidence in each of the direct, indirect, and NMA estimates based on methods developed by the GRADE working group. Using an example of a published NMA, we show...
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