Trial reportPloS one2016
Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study.
Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00789828 (A Randomized, Double-blind, Placebo-controlled Study of Everolimus in the Treatment of Patients With Subependymal Giant Cell Astrocytomas), which is not on this map. Cited by 89 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Placebo-controlled Study of Everolimus in the Treatment of Patients With Subependymal Giant Cell Astrocytomas (SEGA) Associated With Tuberous Sclerosis Complex (TSC)
Who cites it
89 citing papers in PubMed, 3 syntheses or guidelines pooled it, 205 citations in OpenAlex.
- Rapamycin and rapalogs for tuberous sclerosis complex.The Cochrane database of systematic reviews · 2023Pooled it
- Pooled it
- A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC).Orphanet journal of rare diseases · 2020Pooled it
- Effectiveness and safety of everolimus treatment in patients with tuberous sclerosis complex in real-world clinical practice.Orphanet journal of rare diseases · 2023Trial
- A Randomized Multi-institutional Phase II Trial of Everolimus as Adjuvant Therapy in Patients with Locally Advanced Squamous Cell Cancer of the Head and Neck.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Trial
- Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Trial
- Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis-1 with Everolimus: A Phase II, Open-Label, Single-Arm Trial.Drugs in R&D · 2018Trial
- Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex: The TREATMENT Randomized Clinical Trial.JAMA dermatology · 2018Trial
- The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.Pediatric nephrology (Berlin, Germany) · 2018Trial
- Advances in the management of pediatric low-grade glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- The phosphoproteomic landscape of the neurological manifestations in tuberous sclerosis complex.Acta neuropathologica · 2026Article
- Closing the Gap to Interventions for Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): Protocol for a Longitudinal Study of TAND Severity, Predictors, and Caregiver Well-Being (TANDem-2).JMIR research protocols · 2026Article
- Genotype and subependymal lesion burden influence volumetric response to everolimus in tuberous sclerosis complex-associated subependymal giant cell astrocytoma: A 10-year real-world study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Impact of prenatal sirolimus on cardiac rhabdomyomas and brain tubers.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2026Article
- Etiological Analysis and Classification of 108 Patients with Infantile Epileptic Spasms Syndrome Based on the 2017 International League Against Epilepsy Classification.Noro psikiyatri arsivi · 2026Article
- Infantile Spasms (West Syndrome): Integrating Genetic, Neurotrophic, and Hormonal Mechanisms Toward Precision Therapy.Medicina (Kaunas, Lithuania) · 2025Review
- Kidneys in Children with Tuberous Sclerosis Complex-An Up-to-Date Review.Journal of clinical medicine · 2025Review
- State of the art: glioma-associated epilepsy-bridging tumor biology and epileptogenesis.Neurological research and practice · 2025Review
- Late failure of Everolimus in a patient with tuberous sclerosis complex after 10 years of effective response: an illustrative case.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 14 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEverolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828). METHODS AND
findingsEXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m2/day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%).
conclusionsEverolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients.
trial registrationClinicalTrials.gov NCT00789828.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.