In the RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors) phase III study involving patients with pancreatic neuroendocrine tumors (NET), progression-free survival (PFS) in patients treated with everolimus (Afinitor) was more than 6 months longer than for patients taking placebo (11.0 mo vs 4.6 mo, respectively). Data also revealed a 65% reduced risk of cancer progression for patients in the everolimus cohort (hazard ratio, 0.35; 95% confidence interval, 0.27-
0.45; P <.0001).
“Novartis plans to submit worldwide regulatory filings [for a NET indication] in 2010, based on results from the RADIANT-3 study,” said David Lebwohl, MD, vice president and global program head for Afinitor in the Oncology Global Development group at Novartis Oncology. If approved, everolimus would become the first mTOR inhibitor for advanced pancreatic NET, a rare cancer with few therapeutic options and a median overall survival (OS) of 24 months.
The RADIANT-3 prospective, double-blind, parallel group, multicenter study randomized 410 patients with advanced pancreatic NET to 10 mg of oral everolimus or placebo daily Afinitor Active in Pancreatic NET until tumor progression. Following randomization, patients were monitored with CT scanning and MRI approximately every 12 weeks until progression. The primary endpoint was time without tumor growth; secondary endpoints included objective response rate, OS, and levels of biomarkers.
The adverse events pattern in the everolimus arm paralleled prior research results. Patients on everolimus experienced stomatitis (53.9%), rash (52.5%), diarrhea (46.6%), fatigue (43.6%), edema peripheral (35.8%), nausea (31.9%), headache (29.9%), pyrexia (29.4%), decreased appetite (28.9%), vomiting (28.4%), weight loss (27.9%), abdominal pain (23.5%), anemia (22.1%), cough (21.6%) and epistaxis (21.1%).
Study results were presented at the 12th World Congress on Gastrointestinal Cancer in Barcelona, Spain; researchers said they plan to present additional findings later this year at the 35th European Society for Medical Oncology Congress in Milan, Italy. Afinitor is currently FDA-approved as a secondline therapy for patients with advanced renal cell carcinoma following unsuccessful treatment with sunitinib (Sutent) or sorafenib (Nexavar).