About FDA

Everolimus (Accelerated Approval)

On October 29, 2010, the U.S. Food and Drug Administration granted accelerated approval to everolimus (Afinitor, Novartis), an mTOR inhibitor, for patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS) who require therapy but are not candidates for surgical resection. Afinitor was originally approved in March 2009 for the treatment of adult patients with advanced renal cell carcinoma (RCC) whose disease was resistant to sunitinib or sorafenib.

The efficacy and safety of everolimus in patients with SEGA was demonstrated in a single-arm, open-label clinical trial. Twenty-eight patients whose SEGA lesions had demonstrated evidence of growth on serial imaging received everolimus orally once daily at a starting dose of 3 mg/m2/day with subsequent titration to a whole blood concentration of 5-15 ng/mL. The median age was 11 years (range 3-34), 61% were male, and 86% were Caucasian. The primary efficacy endpoint was reduction in the volume of the primary SEGA lesion at 6 months. The median duration of treatment on this trial was 24.4 months (range 4.7-37.3 months).

Nine of 28 patients (32%, 95% CI: 16% - 52%) had a ≥ 50% reduction in the volume of their largest SEGA lesion at 6 months. Three of four patients with a history of prior surgery had greater than 50% reduction in tumor volume. Median response duration for the 9 responding patients was 266 days (range 97 to 946 days). No complete responses were observed.

All patients experienced at least one adverse event. The most common adverse events (incidence > 30%) included stomatitis, upper respiratory tract infections, sinusitis, otitis media, and pyrexia. Grade 3 adverse reactions were reported in 36% of patients and included convulsion, infections (sinusitis, pneumonia, tooth infection, and viral bronchitis), stomatitis, aspiration, cyclic neutropenia, sleep apnea syndrome, vomiting, dizziness, white blood cell count decreased, and neutrophil count decreased. Convulsions (grade 4) were noted in a single patient. No deaths were observed during the study.

Laboratory abnormalities (greater than 30% of patients) included transaminase elevations, hypercholesterolemia and hypertriglyceridemia, leukopenia, anemia, and hyperglycemia.

Live vaccines and close contact with those who have received live vaccines should be avoided.

The recommended starting dose of everolimus for this indication is based on body surface area as shown in the following table with subsequent titration to attain a blood trough concentration of 5-10 ng/mL.

Recommended Starting Dose of Everolimus for Treatment of Patients with SEGA

Body Surface Area (BSA)

Starting Dose

0.5 m2 to 1.2 m2

2.5 mg once daily

1.3 m2 to 2.1 m2

5 mg once daily

Greater than or equal to 2.2 m2

7.5 mg 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).


Page Last Updated: 11/27/2015
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English