On February 26, 2016, the U. S. Food and Drug Administration approved everolimus (Afinitor , Novartis) for the treatment of adult patients with progressive, well-differentiated non-functional, neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease.
Today’s approval was based on demonstration of improvement in progression-free survival (PFS) in a multicenter, randomized (2:1), placebo-controlled trial of everolimus 10 mg orally once daily plus best supportive care (BSC) to placebo plus BSC.
The clinical trial enrolled 302 patients with unresectable, locally advanced or metastatic, well differentiated (low or intermediate grade), non-functional (no current or prior history of carcinoid symptoms), neuroendocrine tumors (NET) of gastrointestinal or lung origin. All patients were required to have evidence of disease progression within 6 months prior to randomization. The major efficacy outcome measure was progression-free survival (PFS) based on independent radiological assessment per RECIST. Median PFS were 11 months and 3.9 months in the everolimus and placebo arms, respectively [HR 0.48 (95% CI: 0.35, 0.67), p <0.001, stratified log rank test]. Overall response rates were 2% in the everolimus arm and 1% in the placebo arm. At the planned interim analysis, there was no statistically significant difference in overall survival between arms.
Safety data were evaluated in 300 patients who received at least one dose of investigational drug. The median exposure duration to everolimus was 9.3 months; 64% of patients were treated for greater than or equal to 6 months and 39% were treated for greater than or equal to12 months.
Everolimus was discontinued for adverse reactions in 29% of patients and dose reduction or delay was required in 70% of everolimus-treated patients. Serious adverse reactions occurred in 42% of everolimus-treated patients and included 3 fatal events (cardiac failure, respiratory failure, and septic shock). The most common adverse reactions (incidence greater than or equal to 30%) were stomatitis, infections, diarrhea, peripheral edema, fatigue and rash. The most common laboratory abnormalities (incidence greater than or equal to 50%) were anemia, hypercholesterolemia, lymphopenia, elevated aspartate transaminase (AST) and fasting hyperglycemia.
The recommended dose and schedule for everolimus is 10 mg orally once daily.
Full prescribing information is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).