Novartis announced that a phase III study of Afinitor (everolimus) tablets plus best supportive care met its primary endpoint, showing the drug significantly extended progression-free survival, or time without tumour growth, in patients with advanced pancreatic neuroendocrine tumours (NET). The study, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumours), is part of the largest clinical trial programme of its kind.

Everolimus is approved under the trade name Afinitor (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.

Pancreatic NET can grow aggressively and at time of diagnosis nearly 60 per cent of all patients have advanced disease, meaning the cancer has spread to other parts of the body and has become more difficult to treat. The median survival rate for patients with advanced pancreatic NET is 17 months. Currently, surgery and chemotherapy are the only approved treatment options for patients with advanced pancreatic NET.

"Everolimus was developed to inhibit the mTOR protein, which is a critical target in treating various cancers, including NET. Results from RADIANT-3 demonstrate that everolimus has the potential to become an important treatment option for patients with advanced pancreatic NET, where there is a major unmet need," said Herve Hoppenot, president, Novartis Oncology. "These study results will serve as the basis of worldwide regulatory filings for everolimus and bring us one step closer to our goal of offering these patients a new therapy."

According to a company release, the full results from the RADIANT-3 study will be submitted for presentation at the European Society for Medical Oncology annual meeting taking place in Milan, Italy in October. Additionally, worldwide regulatory filings are planned for 2010.

RADIANT-3 is a phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multi-centre study. The trial examined the efficacy and safety of everolimus plus best supportive care versus placebo plus best supportive care in 410 patients with advanced pancreatic NET, also known as islet cell tumours. Patients who met the study's entry criteria were randomized 1:1 to receive either daily everolimus (10 mg) or daily placebo orally.

The primary endpoint of RADIANT-3 is progression-free survival. Secondary endpoints include safety, objective response rate and overall survival.

Neuroendocrine tumours arise from cells that can produce and secrete a variety of hormones that regulate bodily functions. There are many types of NET that can occur throughout the body; however, most are found in the gastrointestinal tract, pancreas and lungs. Because NET are relatively rare, there is no routine screening and patients often experience delays of five to seven years before receiving an accurate diagnosis. As a result of this, patients with NET often have advanced disease when diagnosed. Although considered a rare cancer, the incidence of NET is increasing dramatically, having quadrupled in the past 30 years.


In the European Union (EU), everolimus is approved under the trade name Afinitor (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. In the US, Afinitor is approved for the treatment of patients with advanced RCC after failure of treatment with sunitinib or sorafenib.

In the EU, everolimus is available in different dosage strengths under the trade name Certican for the prevention of organ rejection in heart and kidney transplant recipients. In the US, everolimus is available in different dosage strengths under the trade name Zortress for the prevention of rejection of kidney transplants in adult patients at low-to-moderate immunologic risk.

With once-daily dosing, Afinitor works by targeting mTOR in cancer cells, a protein that acts as a central regulator of tumour cell division, blood vessel growth and cell metabolism.