Effect of everolimus on skin lesions in patients treated for subependymal giant cell astrocytoma and renal angiomyolipoma: final 4-year results from the randomized EXIST-1 and EXIST-2 studies.
J Eur Acad Dermatol Venereol
; 32(10): 1796-1803, 2018 Oct.
Article
en En
| MEDLINE
| ID: mdl-29569806
ABSTRACT
BACKGROUND:
Tuberous sclerosis complex (TSC) is a genetic disorder associated with tumour growth in various organs, including the brain, kidneys, heart and skin. Cutaneous lesions are prevalent manifestations of TSC, occurring in up to 90% of patients. Oral mammalian target of rapamycin inhibitors, such as everolimus, is believed to be effective for treatment of TSC-associated lesions because they act on the underlying disease pathophysiology.OBJECTIVE:
We evaluated the long-term effect of oral everolimus on TSC-associated skin lesions as a secondary objective in the phase III studies EXIST-1 (NCT00789828) and EXIST-2 (NCT00790400) after approximately 4 years of treatment. MATERIALS ANDMETHODS:
Everolimus was dosed 4.5 mg/m2 /day (titrated to trough 5-15 ng/mL) in patients with TSC-associated subependymal giant cell astrocytoma in EXIST-1, and 10 mg/day initially in adult patients with TSC- or sporadic lymphangioleiomyomatosis-associated renal angiomyolipoma in EXIST-2. Following positive results from the core phase, remaining patients were offered open-label everolimus in an extension. Skin lesion response rate was the proportion of patients achieving complete or partial clinical response.RESULTS:
A total of 105 patients in EXIST-1 and 107 in EXIST-2 received everolimus and had ≥1 skin lesion at baseline. Skin lesion response rate (95% confidence interval) was 58.1% (48.1-67.7%) in EXIST-1 and 68.2% (58.5-76.9%) in EXIST-2; most were partial responses. At week 192 (EXIST-1 n = 55; EXIST-2 n = 56), 69% and 66% had a response. Most common drug-related adverse event was stomatitis (41-45%).CONCLUSION:
Oral everolimus improved TSC-related skin lesions, with responses sustained over 4 years of treatment in EXIST-1 and EXIST-2.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Astrocitoma
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Neoplasias Cutáneas
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Esclerosis Tuberosa
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Neoplasias del Sistema Nervioso Central
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Angiomiolipoma
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Everolimus
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Neoplasias Renales
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Antineoplásicos
Tipo de estudio:
Clinical_trials
/
Etiology_studies
Límite:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
J Eur Acad Dermatol Venereol
Asunto de la revista:
DERMATOLOGIA
/
DOENCAS SEXUALMENTE TRANSMISSIVEIS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos