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Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations

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  • معلومة اضافية
    • Contributors:
      Cliniques Universitaires Saint-Luc Bruxelles; Institut Roi Albert II; Université Catholique de Louvain = Catholic University of Louvain (UCL)-Cliniques Universitaires Saint-Luc Bruxelles; Université Catholique de Louvain = Catholic University of Louvain (UCL); Institut de Statistique, Biostatistique et Sciences Actuarielles (ISBA); Service de Neuroradiologie CHU Lariboisière; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal APHP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Service de Rhumatologie CHU Lariboisière; Hôpital Lariboisière-Fernand-Widal APHP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Service de Médecine Vasculaire Amiens; CHU Amiens-Picardie; Service de Dermatologie CHU Caen; Université de Caen Normandie (UNICAEN); Normandie Université (NU)-Normandie Université (NU)-CHU Caen; Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN); Institut Desbrest de santé publique (IDESP); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); CHU Montpellier; Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier); WEL Research Institute (WELRI)
    • بيانات النشر:
      HAL CCSD
      American Society for Clinical Investigation
    • الموضوع:
      2023
    • Collection:
      Normandie Université: HAL
    • نبذة مختصرة :
      International audience ; BACKGROUNDSlow-flow vascular malformations frequently harbor activating mutations in the PI3K/AKT/mTOR cascade. Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be evaluated in large prospective phase III trials.METHODSThe Vascular Anomaly-Sirolimus-Europe (VASE) trial, initiated in 2016, is a large multicentric prospective phase III trial (EudraCT 2015-001703-32), which evaluates efficacy and safety of sirolimus for 2 years in pediatric and adult patients with symptomatic slow-flow vascular malformations. In this interim analysis, we studied all patients enrolled up to October 2021 who received sirolimus for 12 or more months or who prematurely stopped the treatment.RESULTSThirty-one pediatric and 101 adult patients were included in this analysis; 107 completed 12 or more months of sirolimus, including 61 who were treated for the whole 2-year period. Sirolimus resulted in a clinical improvement in 85% of patients. The efficacy appeared within the first month for the majority of them. Grade 3-4 adverse events were observed in 24 (18%) patients; all resolved after treatment interruption/arrest. Sirolimus increased feasibility of surgery or sclerotherapy in 20 (15%) patients initially deemed unsuitable for intervention. Among the 61 patients who completed the 2-year treatment, 33 (54%) reported a recurrence of symptoms after a median follow-up of 13 months after sirolimus arrest. While there was no difference in efficacy, clinical improvement was faster but subsided more rapidly in PIK3CA-mutated (n = 24) compared with TIE2-mutated (n = 19) patients.CONCLUSIONSirolimus has a high efficacy and good tolerance in treatment of slow-flow vascular malformations in children and adults.TRIAL REGISTRATIONClinicalTrials.gov NCT02638389 and EudraCT 2015-001703-32.FUNDINGThe Fonds de la Recherche Scientifique (FNRS grants T.0247.19, P.C005.22, T.0146.16, and P.C013.20), the Fund Generet managed by the King Baudouin Foundation (grant ...
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/37937645; PUBMED: 37937645; PUBMEDCENTRAL: PMC10721262
    • الرقم المعرف:
      10.1172/jci.insight.173095
    • الدخول الالكتروني :
      https://hal.science/hal-04284028
      https://hal.science/hal-04284028v1/document
      https://hal.science/hal-04284028v1/file/173095.1-20231020090923-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
      https://doi.org/10.1172/jci.insight.173095
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.75F72A92