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Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis.

ABSTRACT: Background:It remains unknown which is the most effective regimen among the available therapies for advanced well-differentiated neuroendocrine tumors (NETs). We performed a network meta-analysis to address this important issue. Methods:PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR), or odds ratio (OR) and 95% confidence intervals (CIs). Results:Included in the meta-analysis were 21 eligible articles reporting 15 RCTs with a total of 2922 patients randomized to receive 11 treatments. Peptide receptor radionuclide therapy (PRRT) showed significant PFS advantage over somatostatin analogs (SSA) (HR?=?0.21, 95% CI: 0.11-0.41), everolimus (HR?=?0.25, 95% CI: 0.11-0.53), sunitinib (HR?=?0.29, 95% CI: 0.10-0.82), everolimus+SSA (HR?=?0.26, 95% CI: 0.12-0.54), and everolimus+bevacizumab (HR?=?0.31, 95% CI: 0.11-0.82). OS findings were not significantly different between treatments. In terms of treatment rankings of PFS, PRRT had the highest probability (96%) of being the most effective treatment, followed by SSA+bevacizumab (86%) and SSA+interferon-? (IFN-?) (78%). As for toxicity, risk of SAEs was similar between the three treatments. Based on the benefit-risk ratio, PRRT, SSA+bevacizumab, and SSA+IFN-? seemed to be the best, second-, and third-best treatment, respectively. Conclusions:PRRT is likely to be the most preferable treatment for patients with advanced well-differentiated NETs. SSA+bevacizumab and SSA+IFN-? also seem to be more effective regimens with limited risk of SAEs.

SUBMITTER: Liu T

PROVIDER: S-EPMC6542116 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis.

Liu Tingting T Liao Jiehao J Dang Jun J Li Guang G

Therapeutic advances in medical oncology 20190529

<h4>Background</h4>It remains unknown which is the most effective regimen among the available therapies for advanced well-differentiated neuroendocrine tumors (NETs). We performed a network meta-analysis to address this important issue.<h4>Methods</h4>PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall surv ...[more]

PMID: 31191714

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Project description:BackgroundEverolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study.MethodsWe randomly assigned 410 patients who had advanced, low-grade or intermediate-grade pancreatic neuroendocrine tumors with radiologic progression within the previous 12 months to receive everolimus, at a dose of 10 mg once daily (207 patients), or placebo (203 patients), both in conjunction with best supportive care. The primary end point was progression-free survival in an intention-to-treat analysis. In the case of patients in whom radiologic progression occurred during the study, the treatment assignments could be revealed, and patients who had been randomly assigned to placebo were offered open-label everolimus.ResultsThe median progression-free survival was 11.0 months with everolimus as compared with 4.6 months with placebo (hazard ratio for disease progression or death from any cause with everolimus, 0.35; 95% confidence interval [CI], 0.27 to 0.45; P<0.001), representing a 65% reduction in the estimated risk of progression or death. Estimates of the proportion of patients who were alive and progression-free at 18 months were 34% (95% CI, 26 to 43) with everolimus as compared with 9% (95% CI, 4 to 16) with placebo. Drug-related adverse events were mostly grade 1 or 2 and included stomatitis (in 64% of patients in the everolimus group vs. 17% in the placebo group), rash (49% vs. 10%), diarrhea (34% vs. 10%), fatigue (31% vs. 14%), and infections (23% vs. 6%), which were primarily upper respiratory. Grade 3 or 4 events that were more frequent with everolimus than with placebo included anemia (6% vs. 0%) and hyperglycemia (5% vs. 2%). The median exposure to everolimus was longer than exposure to placebo by a factor of 2.3 (38 weeks vs. 16 weeks).ConclusionsEverolimus, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors and was associated with a low rate of severe adverse events. (Funded by Novartis Oncology; RADIANT-3 ClinicalTrials.gov number, NCT00510068.).

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Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis.

Publications

Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis.

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