Researchers have provided interim data on the use of Afinitor (everolimus) for advanced neuroendocrine tumors (NETs) deriving from gastrointestinal (GI) or lung tissue.
Earlier this year, everolimus was approved by the FDA
for the treatment of advanced NETs of GI or lung origin and just a couple days ago, the drug was approved in Europe
. Both approvals were based on the significant difference in progression-free survival seen in the phase 3 RADIANT-4 study.
At the 2016 ASCO Annual Meeting being held in Chicago this week, more data from the pivotal RADIANT-4 study was showing everolimus to have a trend of a overall survival benefit
, though this trend did not meet statistical significance. In addition, a subgroup analysis of patients with NET from GI or unknown tissue showed improvements in survival times
without cancer progression for patients who took the drug.
NET tumors and the RADIANT-4 Study
are arise from cells in the endocrine or nervous system. They most commonly occur in the intestine, but they can also derive from the lung, pancreas, and other parts of the body. Some NET tumors produce symptoms from the secretion of hormones and other sub (GI)stances.
At diagnosis, around 44% of patients with GI NET and 28% of patients with lung NET have cancer spread, making it difficult to treat. Current treatment options for these patients are limited. Everolimus works to decrease cell growth and reproduction. It is already approved to treat a number of other cancers, including certain kinds of breast cancer, and renal cell carcinoma. In the earlier RADIANT-3 trial, everolimus was shown to benefit patients with advanced pancreatic NET tumors.
The RADIANT-4 trial is a randomized, double-blind, placebo-controlled trial of adult patients with advanced, progressive, well-differentiated, non-functional neuroendocrine tumors of the lung or GI tract. Ninety-seven centers in 25 countries are participating in the study. Patients were assigned in a 2:1 ratio to receive supportive care and either 10 mg everolimus per day or a placebo. The primary endpoint of the study is survival without cancer progression, and the secondary endpoint is overall survival.
, the researchers reported on interim outcomes from 302 patients. The study met its primary endpoint, showing a median progression-free survival of 11.0 months for the everolimus group compared to 3.9 months for the placebo group (HR = 0.48).
Additional interim results
The research team presented new data which showed a 27% reduction in the estimated risk of death compared to placebo (HR = 0.73, p = 0.71). In the everolimus group 66 out of 205 patients died compared to 35 of 97 in the placebo group. Though the value did not meet statistical significance, it does suggest a trend toward survival benefit. The estimated survival rate at 2 years was 77% with everolimus and 62% with placebo.
The researchers also presented additional information about progression-free survival in study subgroups. In 175 patients with GI NET, median progression-free survival was 13.1 months compared to 5.4 months for placebo patients, with an estimated 44% risk reduction for the everolimus group (HR = 0.56). In 36 patients with NET of unknown origin, median progression-free survival was 13.6 in those taking the drug compared to 7.5 for placebo (HR = 0.60).
The researchers also reported adverse events associated with the drug. These events (such as diarrhea, hypertension, abdominal pain, acute renal failure) are a known part of the drug’s potential side effects. The RADIANT-4 study is estimated to be completed in August 2017.
Yao JC, Fazio N, Singh S, et al. Everolimus (EVE) in advanced, nonfunctional, well-differentiated neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin: Second interim overall survival (OS) results from the RADIANT-4 study. Poster presented at 2016 ASCO Annual Meeting; Chicago, Il; June 3-6, 2016. Abstract 4090.
Singh S, Carnaghi C, Buzzoni R, et al. Efficacy and safety of everolimus in advanced, progressive, nonfunctional neuroendocrine tumors (NET) of the gastrointestinal (GI) tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial. Poster presented at 2016 ASCO Annual Meeting; Chicago, Il; June 3-6, 2016. Abstract 315.