Neuroendocrine tumors (NETs) describe a heterogeneous group of
tumors with a wide range of morphologic, functional, and behavioral characteristics. These
tumors are generally slow growing and behave in an indolent fashion. However, they have the potential to spread, primarily to the liver and when they do, they can be life threatening and difficult to treat with current modalities. A subset of NETs, the pancreatic
neuroendocrine tumors (
pNET) represent a small percentage of all pancreatic
tumors (1.3%) but their incidence is rising. Prior to 2011, the only approved agent for unresectable
pNETs was
streptozocin (often used in combination with
doxorubicin) but the efficacy of this
drug was questionable. In 2011, the landscape of treatment for
pNET was changed with the approval of the first new agents in 20 years,
sunitinib and
everolimus, that demonstrated improvement in time to progression in patients with progressive
pNET.
Sunitinib is a multikinase inhibitor and
everolimus is an inhibitor of the
mammalian target of rapamycin (mTOR) pathway. These drugs were approved by the Food and Drug Administration (FDA) on the basis of separate large randomized placebo-controlled trials. Data from these two trials and an additional phase III trial looking at
everolimus in other
neuroendocrine tumors has generated intense interest in this challenging disease. At the 2012 American Society of Clinical Oncology (ASCO)
Gastrointestinal Cancers Symposium, several researchers presented updated data regarding the risk stratification, treatment, and outcome for patients with
pNET in the new era of targeted
therapy. Choti et al. (Abstract #187) reviewed demographic data from a large set of patients who presented to National Comprehensive
Cancer Network (NCCN) sites with
neuroendocrine tumors. Casciano et al. (Abstract #226) and Signorovitch et al. (Abstract #237) presented post-approval analysis of the relative role of
everolimus and
sunitinib in the treatment of
pNET. Alistar et al. (Abstract #166) explored predictive
biomarkers in
pNET, and Yao et al. (Abstract #157) conducted multivariate analysis of patients treated with
everolimus in the phase III, RADIANT-2 trial which included the identification of relevant
biomarkers. Hobday et al. (Abstract #260) and Bergsland et al. (Abstract #285) reported phase II data from two clinical trials looking at novel targeted combinations for the treatment of
pNET. Finally the role of treatment for poorly differentiated NETs (including
pNETs) remains ill-defined and Yamaguchi et al. (Abstract #274) presented a report reviewing the experience at 23 centers in Japan in treating this population. The authors review and summarize these abstracts in this article.