Background
Methods
Study design and patients
Treatment
Assessments
Safety assessment
Efficacy assessment
Pharmacokinetics assessment
Statistical analyses
Results
Overall results
n (%) | Everolimus FAS (N = 120) | Everolimus pediatric subpopulation (N = 90) |
---|---|---|
Patients | ||
Completed study | 100 (83.3) | 79 (87.8) |
Discontinued | 20 (16.7) | 11 (12.2) |
Primary reason for premature discontinuation | ||
Adverse event(s) | 8 (6.7) a
| 4 (4.4) |
Otherb
| 5 (4.2) | 3 (3.3) |
Subject withdrew consent | 5 (4.2) | 2 (2.2) |
Administrative problems | 1 (0.8) | 1 (1.1) |
SEGA progression | 1 (0.8) | 1 (1.1) |
Demographic characteristics | Everolimus
N = 120 |
---|---|
Age, median (range), years | 11.0 (1–47) a
|
Sex, n (%) | |
Male | 62 (51.7) |
Female | 58 (48.3) |
Race, n (%) | |
Caucasian | 116 (96.7) |
Asian | 2 (1.7) |
Native American | 1 (0.8) |
Other | 1 (0.8) |
Disease characteristics | Everolimus
N = 120 |
---|---|
Time since TSC diagnosis, median (range), years | 9.1 (0.2–30.7) |
Time since SEGA diagnosis, median (range), years | 3.8 (0–24) |
Modified Gomez criteria - major features, n (%) | |
Facial angiofibromas or forehead plaques | 93 (77.5) |
Non-traumatic ungual or periungual fibroma | 18 (15.0) |
Hypomelanotic macules (3 or more) | 95 (79.2) |
Shagreen patch (connective tissue nevus) | 47 (39.2) |
Multiple retinal nodular hamartomas | 23 (19.2) |
Cortical tuber | 106 (88.3) |
Subependymal nodule | 102 (85.0) |
Subependymal giant cell astrocytoma | 120 (100.0) |
Cardiac rhabdomyoma, single or multiple | 55 (45.8) |
Lymphangioleiomyomatosis | 2 (1.7) |
Renal angiomyolipoma | 59 (49.2) |
Modified Gomez criteria - minor features, n (%) | |
Multiple, randomly distributed pits in dental enamel | 6 (5.0) |
Hamartomatous rectal polyps | 0 (0.0) |
Bone cysts | 2 (1.7) |
Cerebral white matter radial migration lines | 16 (13.3) |
Gingival fibromas | 6 (5.0) |
Non-renal hamartoma | 3 (2.5) |
Retinal achromic patch | 4 (3.3) |
'Confetti' skin lesions | 15 (12.5) |
Multiple renal cysts | 19 (15.8) |
Treatment exposure
Safety
AEs, n (%) | Safety population (N = 120) | Pediatric subpopulation (N = 90) | ||
---|---|---|---|---|
All Grades | Grade 3 or 4 | All Grades | Grade 3 or 4 | |
Patients with any AE(s) | 89 (74.2) | 28 (23.3) | 67 (74.4) | 23 (25.5) |
Preferred term | ||||
Aphthous stomatitis | 18 (15.0) | 2 (1.7) | 13 (14.4) | 1 (1.1) |
Pyrexia | 18 (15.0) | 1 (0.8) | 16 (17.8) | 1 (1.1) |
Bronchitis | 11 (9.2) | 1 (0.8) | 11 (12.2) | 1 (1.1) |
Stomatitis | 10 (8.3) | 4 (3.3) | 7 (7.8) | 4 (4.4) |
Cough | 6 (5.0) | - | 5 (5.6) | - |
Diarrhea | 6 (5.0) | 1 (0.8) | 5 (5.6) | 1 (1.1) |
Headache | 6 (5.0) | 1 (0.8) | 3 (3.3) | 1 (1.1) |
Mouth ulceration | 6 (5.0) | - | 5 (5.6) | - |
Sinusitis | 6 (5.0) | 1 (0.8) | 6 (6.7) | 1 (1.1) |
Abdominal pain | 5 (4.2) | - | 3 (3.3) | - |
Blood creatine phosphokinase increased | 5 (4.2) | 1 (0.8) | 3 (3.3) | 1 (1.1) |
Gastroenteritis | 5 (4.2) | 1 (0.8) | 4 (4.4) | 1 (1.1) |
Hypercholesterolemia | 5 (4.2) | - | - | - |
Pharyngitis | 5 (4.2) | - | 5 (5.6) | - |
Pneumonia | 5 (4.2) | - | 5 (5.6) | - |
Pneumonitis | 5 (4.2) | - | 5 (5.6) | - |
Upper respiratory tract infection | 5 (4.2) | - | 4 (4.4) | - |
Menstruation irregular | 4 (3.3) a
| - | 3 (3.3) | - |
Nasopharyngitis | 4 (3.3) | - | 4 (4.4) | - |
Otitis media | 4 (3.3) | - | 4 (4.4) | - |
Urinary tract infection | 4 (3.3) | - | - | - |
AEs, n (%) | Everolimus
N = 120 |
---|---|
Patients with any AE(s) | 89 (74.2) |
Death | 0 (0.0) |
SAE(s) | 32 (26.7) |
Discontinuation due to AE(s) a
| 8 (6.7) |
AE(s) causing dose adjustment or study drug interruption | 36 (30.0) |
CTC Grade 3 or 4 | 28 (23.3) |
Leading to hospitalization/prolonged hospitalization | 29 (24.2) |
Suspected to be drug related | 62 (51.7) |
Efficacy
Best response according to medical judgment | Everolimus (N = 120), n (%) |
---|---|
Complete response | 0 (0.0) |
Partial response | 81 (67.5) |
Stable disease | 35 (29.2) |
Progressive disease | 1 (0.8) |
Unknown | 3 (2.5) |