The US Food and Drug Administration (FDA) has granted approval to Novartis Oncology's Supplemental New Drug Application (sNDA) for Afinitor to treat patients with pancreatic neuroendocrine tumors.

Afinitor tablets have been approved to treat patients with progressive pancreatic neuroendocrine tumors that are unresectable, locally advanced or metastatic.  The approval was based on a double-blind, randomized, placebo-controlled, phase III trial with progression free survival as the primary endpoint.  This phase III trial was conducted at institutions worldwide and the results were published in the New England Journal of Medicine here.

"The FDA approval of Afinitor represents an important step forward for patients with advanced pancreatic NET," said James Yao, MD, Associate Professor of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. "Patients will now have access to a treatment that has been shown to significantly delay tumor growth and reduce the risk of disease progression."

Afinitor's approval is an important advance in treating pancreatic neuroendocrine tumor patients.  It is the first FDA approved therapy for these patients since 1982.

The Caring for Carcinoid Foundation's (CFCF) Executive Director, Lauren Erb, said "This is a hopeful time for neuroendocrine tumor patients. With the first approval for pancreatic neuroendocrine tumor patients in nearly thirty years, this is an ideal time to redouble our efforts to bring more treatment advances to patients. Neuroendocrine tumor patients deserve safe and effective therapies."

Recently, CFCF funded scientists at Johns Hopkins University identified mutations in the mTOR signaling pathway among patients with non-functioning pancreatic neuroendocrine tumors (Jiao, Shi, Edil, de Wilde, Klimstra, Maitra, Schulick, Tang, Wolfgang, Choti, Velculescu, Diaz, Jr., Vogelstein, Hruban & Papadopoulos, 2011).  Patients with these mutations could be particularly sensitive to mTOR inhibiting drugs like Afinitor.

Any patients considering this or any other potential treatment should consult with a physician well-versed in treating neuroendocrine tumor patients. Experienced clinicians are necessary to understand the best timing and duration of therapy with Afinitor or other potential treatments. Please consult CFCF's Doctor Database or call 617-948-2514 for help finding an experienced clinician.

About Afinitor

Afinitor is an mTOR inhibitor that is currently FDA approved in the United States to treat advanced renal cell carcinoma (2009) and subependymal giant cell astrocytoma (2010 approval) in addition to the most recent approval for neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease.

The mammalian target of rapamycin (mTOR) is a protein that is involved in many cellular pathways including cell growth and death (Reidy, Tang, & Saltz, 2009; Vignot, Faivre, Aguirre, & Raymond, 2008). Targeted therapies called mTOR inhibitors can deactivate mTOR and prevent cellular growth and replication. 

Afinitor can cause serious side effects including lung or breathing problems, infections, and renal failure which can lead to death. Mouth ulcers and mouth sores are common side effects. Afinitor can affect blood cell counts, kidney and liver function, blood sugar and cholesterol levels. Afinitor may cause fetal harm in pregnant women. Women taking Afinitor should not breast feed.

The most common adverse drug reactions (incidence >=15%) are mouth ulcers, rash, diarrhea, fatigue, acneiform dermatitis, infections, weakness, nausea, peripheral swelling, decreased appetite, headache, pneumonitis, abnormal taste, nose bleeds, mucosal inflammation, weight decreases and vomiting. The most common grade 3-4 adverse drug reactions (incidence >=2%) are mouth ulcers, fatigue, decreased white blood cell count, diarrhea, infections, pneumonitis and diabetes mellitus. Cases of hepatitis B reactivation and pulmonary embolism have been reported (Novartis, 2011).  For complete prescribing information please click here.

Yuchen Jiao, Chanjuan Shi, Barish H. Edil, Roeland F. de Wilde, David S. Klimstra, Anirban Maitra, Richard D. Schulick, Laura H. Tang, Christopher L. Wolfgang, Michael A. Choti, Victor E. Velculescu, Luis A. Diaz, Jr., Bert Vogelstein, Kenneth W. Kinzler, Ralph H. Hruban, and Nickolas Papadopoulos (2011). AXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Science, 331(6021), 1199-1203. Retrieved from: http://www.sciencemag.org/content/331/6021/1199.

Novartis media release 2011. Novartis gains FDA approval for Afinitor® as first new treatment in nearly three decades for patients with advanced pancreatic NET.  Retrieved from:http://www.novartis.com/newsroom/media-releases/en/2011/1513095.shtml.

Reidy, D. L., Tang, L. H., Saltz, L. B.  (2009). Treatment of advanced disease in patients with well-differentiated neuroendocrine tumors.  Nature Clinical Practice, Oncology, 6(3), 143-152. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/19190591. 

Vignot, S., Faivre, S., Aguirre, D., Raymond, E. (2005). mTOR-targeted therapy of cancer with rapamycin derivatives. Annals of Oncology, 16(4), 525-537. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/15728109.