The U.S. Food and Drug Administration approved everolimus (Afinitor) for the treatment of adult patients with progressive, well-differentiated non-functional neuroendocrine tumors (NET) of lung or gastrointestinal origin that are unresectable, locally advanced, or metastatic.1
Approval is based on findings from the phase 3 RADIANT-4 trial, which found that everolimus reduced the risk of progression or death by 52% compared with placebo (HR, 0.48; 95% CI, 0.35 – 0.67; P < .00001). Median progression-free survival was 11.0 months (95% CI, 9.2 – 13.3) in the everolimus group vs 3.9 months (95% CI, 3.6 – 7.4) in the placebo arm.
Overall response rates were 2% and 1%, respectively, and there was no statistically significant difference in overall survival between the 2 arms at the planned interim analysis.
In terms of safety, the most frequently reported treatment-related adverse events were stomatitis, infections, diarrhea, peripheral edema, fatigue, and rash. The most common laboratory abnormalities associated with everolimus treatment included anemia, hypercholesterolemia, lymphopenia, elevated AST, and fasting hyperglycemia.
Everolimus was discontinued as a result of toxicity in 29% of patients and the dose was reduced or treatment was delayed in 70% of everolimus-treated patients. A total of 42% of patients experienced serious adverse reactions due to everolimus treatment, including 3 fatalities.
For the international, double-blind study, researchers enrolled 302 patients with advanced, progressive, well-differentiated, non-functional NET of lung or gastrointestinal origin from 97 centers in 25 countries worldwide. Patients were randomly assigned 2:1 to receive everolimus 10 mg per day orally or placebo, both with best supportive care.
The recommended dose and schedule for treatment is 10 mg orally once daily until disease progression or unacceptable toxicity.
Everolimus is also indicated for the treatment of adults with progressive NET of pancreatic origin with unresectable, locally advanced or metastatic disease.
- Everolimus (Afinitor). U.S. Food and Drug Administration website. February 26, 2016. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm488028.htm. Accessed February 26, 2016.