Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis.

Kaderli, Reto Martin; Spanjol, Marko; Kollár, Attila; Bütikofer, Lukas; Gloy, Viktoria; Dumont, Rebecca A; Seiler, Christian A.; Christ, Emanuel R; Radojewski, Piotr; Briel, Matthias; Walter, Martin A (2019). Therapeutic Options for Neuroendocrine Tumors: A Systematic Review and Network Meta-analysis. JAMA oncology, 5(4), pp. 480-489. American Medical Association 10.1001/jamaoncol.2018.6720

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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.

Data Sources

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.

Study Selection

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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Kaderli, Reto Martin, Kollár, Attila, Bütikofer, Lukas (B), Seiler, Christian A.


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services




American Medical Association




Andrea Flükiger-Flückiger

Date Deposited:

05 Mar 2019 17:42

Last Modified:

20 Feb 2024 14:16

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