Targeted Therapies in Pancreatic Neuroendocrine Tumors

Using biologically targeted agents has been a major paradigm shift in the treatment of pancreatic neuroendocrine tumors (pNETs) over the past 5 years. In 2011, the mTOR inhibitor everolimus and the VEGF inhibitor sunitinib were each shown to improve progression-free survival by approximately 6 months. Although an overall survival was not observed with these agents, this endpoint is not expected in patients with pNETs, states Diane Reidy-Lagunes, MD.

These treatments may require a balance of dose reduction and dose escalation to manage toxicities. Following the initiation of therapy, patients may experience mouth sores and fatigue, says Lagunes, but if the dose is reduced or held for a couple of days, patients may begin to tolerate the medication better. Adverse events associated with these agents generally come in phases and do not persist throughout the entire course of treatment, Lagunes adds.

Selecting which agent to begin first depends on patient factors, such as comorbidities, notes Pamela L. Kunz, MD. In most situations, patients will generally receive both agents during the course of therapy. Adverse events of sunitinib include significant fatigue, hypertension, and minor risk of bleeding. Additionally, everolimus can cause hyperglycemia or pneumonitis. As a result, Kunz generally favors sunitinib in an individual with diabetes or lung disease.

MRI or CT scans should be performed more often in the earlier cycles of therapy, says Kunz. Once patients are stable, 6 months may be often enough for scans. If patients are on active treatment, the visits are usually monthly, notes Kunz.