Two New Agents for the Treatment of Pancreatic Neuroendocrine Tumors (PanNETs)
The U.S. Food and Drug Administration (FDA) approved the drugs Sutent (sunitinib) and Afinitor (Everolimus) for the treatment of advanced pancreatic neuroendocrine tumors (PanNETs). Sutent is manufactured by Pfizer, and Afinitor by Novartis. It is exciting to see that the options available for patients with pancreatic neuoendocrine tumors is growing.
Afinitor was approved for the treatment of patients with progressive pancreatic neuroendocrine tumors that are not resectable surgically,that are locally advanced or metastatic. This approval by the FDA was based on a phase III clinical trial of Afinitor, in which the drug was shown to prolong progression free survival in patients with advanced PanNETs. This phase III trial was reported in the New England Journal of Medicine (N Engl J Med. 2011 Feb 10;364(6):514-23.). The research team at Johns Hopkins has played a role in understanding the likely mechanism by which Afinitor works (http://pathology.jhu.edu/pancreas/news.php). The team sequenced all of the known human genes in a series of pancreatic neuroendocrine tumors and found that one in six of these tumors harbors an activating mutation (DNA change) in the mTOR pathway. (Jiao, Shi, Edil, de Wilde, Klimstra, Maitra, Schulick, Tang, Wolfgang, Choti, Velculescu, Diaz, Jr., Vogelstein, Hruban & Papadopoulos, Science, 2011). This is the very pathway that Afinitor targets, and it is likely that Afinitor will be most effective in patients with a tumor with an mTOR pathway gene mutation.
Sunitinib belongs to the class of drugs called “tyrosine kinase inhibitors,” and it has both effects against blood vessels in tumors (antiangiogenic) and effects against the tumor itself (antitumor properties). In a phase III clinical trial treatment with Sunitinib has been shown to significantly improve progression free survival in patients with metastatic pancreatic neuroendocrine tumors (PNETs) (Reviewed in: Cancer Metastasis Rev, 2011, Suppl 1:19-26).
We are excited by these new agents and look forward to new advances in the treatment of patients with pancreatic neuroendocrine tumors. To learn more about pancreatic neuroendocrine tumors visit: http://pathology.jhu.edu/pancreas/TreatmentEndocrine.php