Phase III trial of Afinitor (everolimus) to treat neuroendocrine tumors (NET) of GI or lung origin- Novartis

Novartis announced results of a Phase III pivotal study showing Afinitor (everolimus) tablets reduced the risk of progression by 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.35-0.67; p<0.00001) vs placebo in patients with advanced, progressive, nonfunctional neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin.

The study, RADIANT-4, will be presented at the European Cancer Congress (ECC) 2015 in Vienna, Austria, and was highlighted in the ECC press conference on Saturday, September 26.

Additionally, the data show everolimus, a mammalian target of rapamycin (mTOR) inhibitor, extended median progression free survival (PFS) by 7.1 months: median PFS by central review was 11.0 months (95% CI, 9.2–13.3) in the everolimus arm and 3.9 months (95% CI, 3.6–7.4) in the placebo arm. Overall survival (OS) was a key secondary endpoint of the trial. While the OS data are not mature, the first interim analysis showed a trend favouring the everolimus arm. Additional OS analyses are planned. Another secondary endpoint was best overall response rate; the study found that 64% of patients receiving everolimus experienced at least some degree of tumour shrinkage compared to 26% of those on placebo. Safety was also a secondary endpoint of the trial and adverse events (AEs) were consistent with the known safety profile of everolimus.

Comment: 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 GI 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. The most recent available data show that in 2004, NET were diagnosed in approximately five cases per 100,000 per year. Although considered a rare cancer, the incidence of NET is increasing dramatically, having more than quadrupled in the past 30 years.

Comment: The results of the RADIANT-4 study – part of the largest clinical trial programme in patients with advanced NET – will serve as the basis of worldwide regulatory submissions for Afinitor for the treatment of advanced, progressive, nonfunctional GI and lung NET. Afinitor is already approved in more than 95 countries worldwide for locally-advanced, metastatic or unresectable progressive NET of pancreatic origin.