From the Journals

Meta-analysis: Combo therapies best for neuroendocrine tumors

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Comparison studies needed, commentators say

One question that remains from the study by Reto M. Kaderli, MD, and his colleagues is the comparative advantages and disadvantages of the various therapies used to treat patients with neuroendocrine tumors.

Recently, several novel therapies have been approved for the treatment of pancreatic and gastrointestinal neuroendocrine tumors, which include agents used for both tumor and symptom control. The majority of studies that evaluated these agents compared them with a comparator of unclear efficacy or placebo. As a result, it is challenging to compare and contrast these competing therapies with respect to efficacy and safety.

Other challenges also exist, such as the biological and clinical diversity seen with neuroendocrine tumors. The current body of literature contains studies that examined different tumor types, including pancreatic, midgut, or gastroenteropancreatic neuroendocrine tumors, which caused significant variation in outcomes. Similar difficulties were seen with the response criteria across these studies.

These results support the active recruitment of patients into randomized comparison studies, which compare these therapies directly. While these types of studies will require larger sample sizes versus placebo-controlled trials, they are necessary to better understand which agents are best in different subtypes of neuroendocrine tumors.

Jonathan R. Strosberg, MD, and Taymeyah Al-Toubah, MPH, are affiliated with the department of gastrointestinal oncology at H. Lee Moffitt Cancer Center and Research Institute in Tampa. Mauro Cives, MD, is affiliated with the department of biomedical sciences and human oncology at the University of Bari in Italy. Dr. Strosberg reported having financial affiliations with Ipsen, Lexicon, and Novartis. These comments are adapted from their accompanying editorial (JAMA Oncol. 2019 Feb 14. doi: 10.1001/jamaoncol.2018.6694 .


 

FROM JAMA ONCOLOGY

Multiple treatment options, which have shown to be safe and effective for patients with neuroendocrine tumors (NET), are presently available, according to a systematic review and meta-analysis of 30 randomized clinical trials.

“We aimed to identify all [randomized clinical trials] comparing therapeutic interventions in [neuroendocrine tumors],” Reto M. Kaderli, MD, of the University of Bern in Switzerland, and his colleagues wrote in JAMA Oncology.

The researchers searched major databases for studies that compared treatment options for patients with neuroendocrine tumors. After applying the search criteria, the team found 38 studies that included a total of 30 randomized trials.

Various outcome measures were used, including progression-free survival, overall survival, disease control, quality of life, and adverse events. The majority of studies compared an intervention to a comparator of unclear efficacy or placebo. In addition, Dr. Kaderli and his colleagues completed a network meta-analysis to analyze the efficacy of each treatment option.

“The results suggest a superiority of combination therapies, especially of those including somatostatin analogues. In pNETs [pancreatic NETs], somatostatin analogues plus interferon, everolimus, or everolimus plus bevacizumab were highly efficacious. The certainty of evidence for these therapies was variable and was the highest for somatostatin analogues plus everolimus,” Dr. Kaderli and his associates wrote.

Furthermore, the results “suggest a range of monotherapies that are superior to placebo, including everolimus, interferon, and sunitinib in pNETs, and somatostatin analogues in pNETs and GI [gastrointestinal]-NETs,” they said.

The researchers acknowledged that a key limitation of the study was the inability to acquire unpublished data. Consequently, Dr. Kaderli and his colleagues reported there may be a risk of publication bias.

The study was supported by funding from the Insula Stiftung zur Förderung der viszeralchirurgischen Forschung. The authors reported no conflicts of interest.

SOURCE: Kaderli RM et al. JAMA Oncol. 2019 Feb 14. doi: 10.1001/jamaoncol.2018.6720.

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