What is the available evidence on therapies for neuroendocrine tumors?
This systematic review and network meta-analysis identified 30 relevant randomized clinical trials comprising 3895 patients with neuroendocrine tumors assigned to 22 different therapies. A network meta-analysis identified 7 therapies for pancreatic neuroendocrine tumors and 5 therapies for gastrointestinal neuroendocrine tumors with a broad range of different toxic effects and higher efficacy than placebo.
There appears to be a range of efficient therapies with different safety profiles available for patients with neuroendocrine tumors.
Multiple therapies are currently available for patients with neuroendocrine tumors (NETs), yet many therapies have not been compared head-to-head within randomized clinical trials (RCTs).
To assess the relative safety and efficacy of therapies for NETs.
PubMed, Embase, the Cochrane Central Register of Controlled Trials, trial registries, meeting abstracts, and reference lists from January 1, 1947, to March 2, 2018, were searched. Key search terms included neuroendocrine tumors, gastrointestinal neoplasms, therapy, and randomized controlled trial.
Randomized clinical trials comparing 2 or more therapies in patients with NETs (primarily gastrointestinal and pancreatic) were evaluated. Thirty RCTs met the selection criteria.
Data Extraction and Synthesis
Pairs of independent reviewers screened studies, extracted data, and assessed the risk of bias. A network meta-analysis with a frequentist approach was used to compare the efficacy of therapies; the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used.
Main Outcomes and Measures
Disease control, progression-free survival, overall survival, adverse events, and quality of life.
The systematic review identified 30 relevant RCTs comprising 3895 patients (48.4% women) assigned to 22 different therapies for NETs. These therapies showed a broad range of risk for serious and nonserious adverse events. The network meta-analyses included 16 RCTs with predominantly a low risk of bias; nevertheless, precision-of-treatment estimates and estimated heterogeneity were limited. The network meta-analysis found 7 therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.35 [95% CI, 0.28-0.45]), everolimus plus somatostatin analogue (HR, 0.35 [95% CI, 0.25-0.51]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.44 [95% CI, 0.26-0.75]), interferon (HR, 0.37 [95% CI, 0.16-0.83]), interferon plus somatostatin analogue (HR, 0.31 [95% CI, 0.13-0.71]), somatostatin analogue (HR, 0.46 [95% CI, 0.33-0.66]), and sunitinib (HR, 0.42 [95% CI, 0.26-0.67]), and 5 therapies for gastrointestinal NETs: bevacizumab plus somatostatin analogue (HR, 0.22 [95% CI, 0.05-0.99]), everolimus plus somatostatin analogue (HR, 0.31 [95% CI, 0.11-0.90]), interferon plus somatostatin analogue (HR, 0.27 [95% CI, 0.07-0.96]), Lu 177–dotatate plus somatostatin analogue (HR, 0.08 [95% CI, 0.03-0.26], and somatostatin analogues (HR, 0.40 [95% CI, 0.21-0.78]) with higher efficacy than placebo and suggests an overall superiority of combination therapies.
Conclusions and Relevance
The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs.
Kaderli RM, Spanjol M, Kollár A, et al. Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis. JAMA Oncol. Published online February 14, 20195(4):480–489. doi:10.1001/jamaoncol.2018.6720
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