Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study

Franz, David Neal; Ed, Belousova; Sparagana, Steven; Bebin, E. Martina; Frost, Michael; Kuperman, Rachel; Witt, Olaf; Kohrman, Michael; Flamini, J. Robert; Wu, Joyce; Curatolo, Paolo; Vries, Petrus J. de; Berkowitz, Noah; Anak, Oezlem; Niolat, Julie; Jóźwiak, Sergiusz

doi:10.1016/s1470-2045(14)70489-9

Cited by 154 publications

(113 citation statements)

References 28 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…All patients remaining in the study were then offered open‐label everolimus for up to 4 years in an extension phase. A recently published interim analysis, which includes 111 patients who received ≥ 1 dose of everolimus, has also demonstrated sustained efficacy on SEGA tumor reduction 30. Including both the primary and extension phases, patients had been exposed to everolimus for a median of 29.3 months, which is similar to the exposure reported in the previous long‐term analysis for our study 13, 30.…”

Section: Discussionsupporting

confidence: 74%

“…Including both the primary and extension phases, patients had been exposed to everolimus for a median of 29.3 months, which is similar to the exposure reported in the previous long‐term analysis for our study 13, 30. Approximately 47% of the patients (36 of 76) experienced clinically meaningful reductions (≥50%) in SEGA volume at 96 weeks (∼22 months); this is very similar to the 50% of patients achieving the same response at 24 months in our study 13, 30. We expect that the conclusion of the extension phase of the EXIST‐1 study in the coming year will further support the findings from this final ≥5‐year analysis.…”

Section: Discussionsupporting

confidence: 69%

“…A recently published interim analysis, which includes 111 patients who received ≥ 1 dose of everolimus, has also demonstrated sustained efficacy on SEGA tumor reduction 30. Including both the primary and extension phases, patients had been exposed to everolimus for a median of 29.3 months, which is similar to the exposure reported in the previous long‐term analysis for our study 13, 30. Approximately 47% of the patients (36 of 76) experienced clinically meaningful reductions (≥50%) in SEGA volume at 96 weeks (∼22 months); this is very similar to the 50% of patients achieving the same response at 24 months in our study 13, 30.…”

Section: Discussionmentioning

confidence: 95%

See 2 more Smart Citations

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Franz

Agricola

Mays

et al. 2015

Annals of Neurology

Self Cite

144

View full text Add to dashboard Cite

ObjectiveTo analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open‐label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this ≥5‐year analysis.MethodsPatients aged ≥ 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (≥2 magnetic resonance imaging scans) received everolimus starting at 3mg/m2/day (titrated to target blood trough levels of 5–15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume.ResultsAs of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7–83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of ≥50% and ≥30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study.InterpretationEverolimus continues to demonstrate a sustained effect on SEGA tumor reduction over ≥5 years of treatment. Everolimus remained well‐tolerated, and no new safety concerns were noted. Ann Neurol 2015;78:929–938

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Everolimus for subependymal giant cell astrocytoma: 5‐year final analysis

Franz

Agricola

Mays

et al. 2015

Annals of Neurology

Self Cite

144

View full text Add to dashboard Cite

show abstract

“…A recent review article indicated that TSC-associated neuropsychiatric symptoms are rarely assessed and treated, suggesting that these management should be coordinated with treatment of other organ systems [30]. Although everolimus induced significant reduction of SEGA size [31], a previous clinical study reported that everolimus [32]. Moreover, everolimus's effect is not easily characterized within TSC lesion such as SEGA and AML [32].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Everolimus on Core Autism Symptoms and Increasing Serum Ceruloplasmin and Transferrin Levels in a Pubescent Boy with Tuberous Sclerosis

Yui¹,

Imataka²,

Okanishi³

et al. 2017

Neonat Pediatr Med

View full text Add to dashboard Cite

show abstract

“…Especially in the brain, the resulting growth is problematic, causing mental defects especially autism, low intelligence, and epilepsy [26]. Accordingly mTORC1 inhibition has revolutionized the clinical management of TSC [27]. mTORC1 inhibition, however, fails to resolve disease completely, leading to the suspicion that other TSC-protein dependent pathways should exist.…”

Section: Peptide Arraying Remains Dominant For Kinome Profilingmentioning

confidence: 99%