The FINANCIAL — Novartis announced on September 27 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 tumors (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, 9.23-13.3) in the everolimus arm and 3.9 months (95% CI, 3.58-7.43) 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 favoring 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 tumor shrinkage compared to 26% of those on placebo, according to Novartis.
Safety was also a secondary endpoint of the trial and adverse events (AEs) were consistent with the known safety profile of everolimus. The most common treatment-related grade 3/4 AEs (>5%) for everolimus and placebo, respectively, were stomatitis (9.0% vs 0.0%), diarrhea (7.0% vs 2.0%) and infections (7.0% vs 0.0%).
“Advanced, progressive, nonfunctional NET of GI or lung origin are rare and aggressive cancers, with limited treatment options,” said James Yao, MD, Professor of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, and the study’s principal investigator. “These pivotal trial results demonstrate strong evidence for the efficacy of the mTOR inhibitor everolimus in this patient population.”
NET are a rare type of cancer that originate in neuroendocrine cells found throughout the body, and are most often found in the GI tract, lungs or pancreas. NET can be functional or nonfunctional: functional NET produce symptoms caused by the secretion of hormones and other substances; nonfunctional NET may produce symptoms caused by the tumor’s growth, such as intestinal blockage, pain and bleeding. At time of diagnosis, 5%-44% of patients with NET in the GI system and 28% of patients with lung NET have advanced disease, meaning the cancer has spread to other parts of the body and is more difficult to treat.
“These results show that everolimus has the potential to be a new, clinically meaningful therapy for patients with advanced, progressive, nonfunctional GI or lung NET, which typically have poor prognoses,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “Our work with the RADIANT clinical program demonstrates our long-term commitment to NET and has yielded important data that have led to improved outcomes for patients with different types of NET.”
The results of the RADIANT-4 study-part of the largest clinical trial program 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.