FDA has approved everolimus (Afinitor, Novartis) tablets to treat patients with progressive neuroendocrine tumors of pancreatic origin that cannot be removed by surgery or that have spread to other parts of the body.
FDA has approved everolimus (Afinitor, Novartis) tablets to treat patients with progressive neuroendocrine tumors (NET) of pancreatic origin (PNET) that cannot be removed by surgery or that have spread to other parts of the body (metastatic).
Afinitor targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth, and cell metabolism. Preclinical and clinical data have established the role of mTOR in the development and progression of several types of tumors, including advanced PNET.
It is the first new treatment in nearly 3 decades for patients with advanced pancreatic PNET. It is estimated that there are fewer than 1,000 new cases in the United States each year.
The approval was based on phase 3 data from the RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors) trial in 410 patients with metastatic or locally advanced disease. The trial showed treatment with Afinitor more than doubled the time without tumor growth (median 4.6 to 11.0 months) and reduced the risk of cancer progression by 65% when compared with placebo in patients with advanced pancreatic NET (HR=0.35; 95% CI, 0.27–0.45; P<.001). A consistent improvement in progression-free survival was seen with Afinitor in all patient subgroups. FDA determined that the safety and effectiveness of Afinitor in the treatment of patients with carcinoid tumors have not been established.
“The approval of everolimus marks an important advance for the treatment of pancreatic neuroendocrine tumors,” James C. Yao, MD, associate professor and deputy chair, Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, told Formulary. “It is the only approval based on statistically significant and clinically meaningful results from a phase III study. Previously available therapies often had limited efficacy or unfavorable toxicity profile. For example, many regional therapy options carried significant risks and required hospitalization. Everolimus targets specific and relevant molecular abnormalities in pancreatic neuroendocrine tumor and presents a novel evidenced-based treatment for this group of patients with unmet medical need.”
In patients treated with Afinitor for neuroendocrine pancreatic tumors, the most commonly reported side effects included inflammation of the mouth (stomatitis), rash, diarrhea, fatigue, edema, abdominal pain, nausea, fever, and headache.
Afinitor is also approved to treat patients with kidney cancer (advanced renal cell carcinoma), after they fail treatment with Sutent (sunitinib) or Nexavar (sorafenib), and patients with subependymal giant cell astrocytoma (a type of brain cancer) associated with tuberous sclerosis, who cannot be treated by surgery.
Afinitor has another trade name, Zortress, and is approved to treat certain adult patients to prevent organ rejection after a kidney transplant. Zortress has a different safety profile in these patients.