Everolimus, an mTOR inhibitor, dramatically improved progression-free survival in patients with advanced, non-functional neuroendocrine tumors of the lung and gastrointestinal tract, according to results of the RADIANT-4 trial presented September 27, 2015 at The European Cancer Congress 2015 in Vienna, Austria.
This news is particularly meaningful for patients with neuroendocrine tumors (NETs) of the lung because there is currently no approved treatment for such cases.
“Although we knew from previous studies that everolimus could delay the growth of pancreatic NETs, this is the first time we have been able to conclusively show that it is effective in other NET sites,” said James C. Yao, MD, professor and chair of the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, in Houston, Texas.
The incidence of NETs is 5.25 per 100,000, with the occurrence on the rise, Dr. Yao said. More than 51% of NETs appear in the GI tract, 27% in the lungs, and 6% in the pancreas, according to data from population-based registries.
Dr. Yao explained that non-functional NETs either don’t secret a hormone or secrete one that doesn’t cause symptoms, so they’re often diagnosed later when the cancer has become advanced. “About 80% of all NETs are thought to be non-functional, so unfortunately late diagnosis is common and poses a major problem for these patients,” he said.
Everolimus is an immunosuppressant drug currently marketed as Zortress® by Novartis to prevent rejection of organ transplants, but it also has anti-angiogenic properties. It inhibits the mTOR protein, a central regulator of tumor cell division and blood vessel growth in cancer cells.
"We became interested in everolimus because we noticed a number of genetic cancer syndromes in the mTOR pathway were associated with neuroendocrine tumors, and others also found that the dysregulation of this pathway in sporadic tumors is also linked to poor prognosis,” Dr. Yao explained.
In this international double-blind trial, Dr. Yao and colleagues enrolled 302 patients (median age 63) with advanced, nonfunctional NETs of the lung or GI tract. The investigators randomized 205 patients to receive 10 mg of everolimus and 97 to receive placebo. Both groups were well matched for prior therapy. The most common tumor sites included non-fuctional NETs of the lung (30%) and the small intestine (24%). The primary endpoint was progression-free survival.
“We found a statistically significant 52% reduction in the risk of progression or death in favor of everolimus, and also a clinically meaningful 2.8-fold (7.1 months) improvement in median progression-free survival compared with those who had taken placebo. In addition, everolimus was well tolerated by the patients and its safety profile was good,” Dr. Yao said.
Interim results also showed a trend toward improved overall survival—but it’s too soon to make a definitive conclusion, he added.
“We were pretty confident that the drug would be active in this broader range of neuroendocrine tumors, but the magnitude of the treatment benefit is wonderful to see—even stronger than we saw in previous studies,” Dr. Yao said. “The field of treating these diseases has changed so drastically over the last decade, and to be able to potentially offer patients for whom there were no options a therapeutic benefit is very exciting.”