Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma

Krueger, Darcy A.; Caré, Marguerite M.; Agricola, Karen; Tudor, Cindy; Mays, Maxwell; Franz, David Neal

doi:10.1212/wnl.0b013e3182815428

Cited by 184 publications

(163 citation statements)

References 23 publications

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“…Along with the results from our previously published interim report,13 this final 5‐year extension of our prospective open‐label study8 confirms the sustained efficacy of everolimus in reducing SEGA tumor burden. Long‐term everolimus treatment prevented tumor growth and reduced SEGA volume in at least 1 instance in all patients.…”

Section: Discussionsupporting

confidence: 81%

“…A total of 6 patients discontinued during the course of the study (Fig 1). As reported previously, 3 patients withdrew consent at 4.7, 17.5, and 21.5 months for noncompliance with antiepileptic drug, inability to maintain study visits, and withdrawal of parental consent, respectively 8, 13. Since the previous analysis, 1 patient was lost to follow‐up (at 31.8 months), 1 patient discontinued for personal reasons (at 60 months), and 1 patient died (at 62.6 months) due to sudden unexplained death in epilepsy.…”

Section: Resultsmentioning

confidence: 84%

“…Although 6 patients did not complete the study, none of them discontinued treatment due to a drug‐related AE and no new safety concerns have arisen since the previous analyses 8, 13. No patients developed major renal impairments in the current study.…”

Section: Discussionmentioning

confidence: 81%

“…The design of our prospective, nonrandomized, open‐label study has been described in detail previously 8, 13. Twenty‐eight patients were enrolled and received oral everolimus during a 6‐month core phase (primary analysis; data cutoff = December 9, 2009) 8.…”

Section: Methodsmentioning

confidence: 99%

“…The study was initiated on January 7, 2007; previously published interim results of a ≥2‐year analysis (data cutoff = December 31, 2010) have demonstrated sustained reduction of SEGA volume with everolimus over that time period 13. Updated efficacy and safety data became available after the study completion date of January 28, 2014, and results of the final ≥5‐year analysis are presented herein.…”

mentioning

confidence: 99%

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

Franz

Agricola

Mays

et al. 2015

Annals of Neurology

144

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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

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Section: Discussionsupporting

confidence: 81%

Section: Resultsmentioning

confidence: 84%