Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Researchers have reviewed the efficacy and safety of common treatments for neuroendocrine tumours (NETs), which they believe may help pave the way for the development of clinical guidelines and head-to-head clinical trials.
“The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs”, say Martin Walter, from the University of Geneva in Switzerland, and co-authors in JAMA Oncology.
Moreover, the analysis pointed to “overall superiority of combination therapies” for the treatment of NETs, they report.
The team identified 30 randomised clinical trials of 22 treatments, including 3895 patients. The trials were performed in 41 different countries between 1980 and 2018. Overall, 68% of the trial publications were free from a high risk of bias for selection, performance, detection, attrition and selective reporting, the researchers write.
Analysis of progression-free survival (PFS) in eight trials comparing nine treatments for pancreatic NETs demonstrated a significant benefit versus placebo for interferon plus somatostatin analogue (SSA; HR=0.31), everolimus plus SSA (HR=0.35), everolimus monotherapy (HR=0.35), interferon (HR=0.37), sunitinib (HR=0.42), everolimus plus bevacizumab and SSA (HR=0.44) and SSA monotherapy (HR=0.56), but not dactolisib monotherapy.
Similarly, the team analysed data for eight different therapies tested in eight trials of GI NET patients, and found a PFS benefit with 177Lu-dotatate plus SSA (HR=0.08), bevacizumab plus SSA (HR=0.22), interferon plus SSA (HR=0.27) and everolimus plus SSA (HR=0.31) and SSA monotherapy (HR=0.40). But no significant benefit versus placebo was found for single agent use of everolimus or interferon in this group.
Analysis of quality of life and safety showed a “broad range of risk for adverse events and effects on quality of life”, the researchers say, with the rate of grade 3–4 adverse events ranging from 3.0% for patients given interferon plus SSA to 68.4% for use of everolimus plus SSA and 83.9% for those given dactolisib.
Just 37% of the trials and subgroup analyses examined were included in the latest guidelines, such as those published by the ENETS and NANETS, and some highly effective combinations, such as everolimus plus SSA, are not widely recommended, the researchers note.
“This overview of what we believe to be the most pertinent and current evidence demonstrates a range of efficient therapies with different safety profiles that are available for patients with NETs and may facilitate informed clinical decision making, drafting of guidelines, and planning of future research”, conclude Martin Walter and co-workers.
Kaderli RM, Spanjol M, Kollár A, et al. Therapeutic options for neuroendocrine tumors. A systematic review and network meta-analysis. JAMA Oncol; Advance online publication 14 February 2019. doi:10.1001/jamaoncol.2018.6720
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