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74 The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma
74 - The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis... Page 1 of 2
e74 The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma 1
2
3
4
5
Jozwiak S. , Belousova E. , Kingswood C. , Frost M. , Kuperman R. , 6
7
8
9
10
Bebin M. , Korf B. , Flamini R. , Kohrman M. , Sparagana S. , Wu 11
12
12
J. , Sahmoud T. , Shah G. , Franz D. 1
13
The Children's Memorial Health Institute of Warsaw, Dept. of Child 2
Neurology, Warsaw, Poland, Moscow Research Institute of Pediatrics & Pediatric Surgery, , Moscow, Russia,
3
Royal Sussex County 4
Hospital , Sussex Renal Unit, Brighton, United Kingdom, Minnesota Epilepsy Group, , St. Paul, Minnesota, United States of America, 5
Children's Hospital and Research Center Oakland, Dept. of 6
Neurology, Oakland, California, United States of America, University of Alabama School of Medicine, Dept. of Neurology, Birmingham, 7
Alabama, United States of America, University of Alabama at Birmingham, Dept. of Genetics, Birmingham, Alabama, United States of America,
8
Children’s Healthcare of Atlanta, , Atlanta, Georgia, 9
United States of America, University of Chicago and Comer Children’s Hospital, , Chicago, Illinois, United States of America, 10
Texas Scottish Rite Hospital For Children, , Dallas, Texas, United 11
Mattel Children’s Hospital at UCLA, Dept. of States of America, Pediatric Neurology, Los Angeles, California, United States of America, 12
Novartis Pharmaceuticals Corporation, , Florham Park, New Jersey, 13
United States of America, Cincinnati Children's Hospital Medical Center, Dept. of Pediatrics and Neurology, Cincinnati, Ohio, United States of America INTRODUCTION & OBJECTIVES: To evaluate the activity of oral
file://F:\RamShankar\April\04-05-12\Cip\Sour\74.html
4/7/2012
74 - The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis... Page 2 of 2
e74a everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma (AML) lesions in patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). MATERIAL & METHODS: A prospective, double-blind, randomized, placebo-controlled, phase 3 study, EXIST-1 (NCT00789828), examined the effects of everolimus in patients with SEGA associated with TSC. Patients with serial SEGA growth from prebaseline to baseline scans were randomized in a 2:1 scheme to receive everolimus (n=78) or placebo (n=39) stratified by use of enzymeinducing anti-epileptic drugs. The starting dose of everolimus was 4.5 2
mg/m /day and was adjusted to a trough level of 5-15 ng/mL based on patient tolerability. Exploratory analysis of AML response rates was performed in patients (n=44) with >1 target baseline AML lesion with longest diameter >1.0 cm. AML response rate, defined as the proportion of patients with confirmed AML response (reduction in total target AML volume >50% from baseline), was assessed by kidney CT or MRI screening at baseline, 12, 24, and 48 weeks, and then annually. RESULTS: The AML response rate was 53.3% (16/30) and 0% (0/14) for everolimus- and placebo-treated patients, respectively. AML reductions >50% were seen only in everolimus-treated patients (56.5%, 78.3%, 80%) compared with placebo-treated patients (0% at each time point) at week 12, 24, and 48, respectively. Greater percentages of everolimus-treated patients had AML reductions >30% at these same time points (82.6%, 100%, 100% vs. 8.3%, 18.2%, 16.7% for everolimus- and placebo-treated patients, respectively). CONCLUSIONS: Everolimus therapy showed efficacy in reducing AML lesion volume in patients with SEGA associated with TSC who also presented with AML. It may offer a pharmacological treatment option for patients with TSC and concomitant AML and SEGA.
file://F:\RamShankar\April\04-05-12\Cip\Sour\74.html
4/7/2012
e74 The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma 1
2
3
4
5
Jozwiak S. , Belousova E. , Kingswood C. , Frost M. , Kuperman R. , 6
7
8
9
10
Bebin M. , Korf B. , Flamini R. , Kohrman M. , Sparagana S. , Wu 11
12
12
J. , Sahmoud T. , Shah G. , Franz D. 1
13
The Children's Memorial Health Institute of Warsaw, Dept. of Child 2
Neurology, Warsaw, Poland, Moscow Research Institute of Pediatrics & Pediatric Surgery, , Moscow, Russia,
3
Royal Sussex County 4
Hospital , Sussex Renal Unit, Brighton, United Kingdom, Minnesota Epilepsy Group, , St. Paul, Minnesota, United States of America, 5
Children's Hospital and Research Center Oakland, Dept. of 6
Neurology, Oakland, California, United States of America, University of Alabama School of Medicine, Dept. of Neurology, Birmingham, 7
Alabama, United States of America, University of Alabama at Birmingham, Dept. of Genetics, Birmingham, Alabama, United States of America,
8
Children’s Healthcare of Atlanta, , Atlanta, Georgia, 9
United States of America, University of Chicago and Comer Children’s Hospital, , Chicago, Illinois, United States of America, 10
Texas Scottish Rite Hospital For Children, , Dallas, Texas, United 11
Mattel Children’s Hospital at UCLA, Dept. of States of America, Pediatric Neurology, Los Angeles, California, United States of America, 12
Novartis Pharmaceuticals Corporation, , Florham Park, New Jersey, 13
United States of America, Cincinnati Children's Hospital Medical Center, Dept. of Pediatrics and Neurology, Cincinnati, Ohio, United States of America INTRODUCTION & OBJECTIVES: To evaluate the activity of oral
file://F:\RamShankar\April\04-05-12\Cip\Sour\74.html
4/7/2012
74 - The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis... Page 2 of 2
e74a everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma (AML) lesions in patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). MATERIAL & METHODS: A prospective, double-blind, randomized, placebo-controlled, phase 3 study, EXIST-1 (NCT00789828), examined the effects of everolimus in patients with SEGA associated with TSC. Patients with serial SEGA growth from prebaseline to baseline scans were randomized in a 2:1 scheme to receive everolimus (n=78) or placebo (n=39) stratified by use of enzymeinducing anti-epileptic drugs. The starting dose of everolimus was 4.5 2
mg/m /day and was adjusted to a trough level of 5-15 ng/mL based on patient tolerability. Exploratory analysis of AML response rates was performed in patients (n=44) with >1 target baseline AML lesion with longest diameter >1.0 cm. AML response rate, defined as the proportion of patients with confirmed AML response (reduction in total target AML volume >50% from baseline), was assessed by kidney CT or MRI screening at baseline, 12, 24, and 48 weeks, and then annually. RESULTS: The AML response rate was 53.3% (16/30) and 0% (0/14) for everolimus- and placebo-treated patients, respectively. AML reductions >50% were seen only in everolimus-treated patients (56.5%, 78.3%, 80%) compared with placebo-treated patients (0% at each time point) at week 12, 24, and 48, respectively. Greater percentages of everolimus-treated patients had AML reductions >30% at these same time points (82.6%, 100%, 100% vs. 8.3%, 18.2%, 16.7% for everolimus- and placebo-treated patients, respectively). CONCLUSIONS: Everolimus therapy showed efficacy in reducing AML lesion volume in patients with SEGA associated with TSC who also presented with AML. It may offer a pharmacological treatment option for patients with TSC and concomitant AML and SEGA.
file://F:\RamShankar\April\04-05-12\Cip\Sour\74.html
4/7/2012