PIK3CA-related overgrowth spectrum (PROS) includes rare genetic conditions due to gain-of-function mutations in the PIK3CA gene. There is no approved medical therapy for patients with PROS, and alpelisib, an approved PIK3CA inhibitor in oncology, showed promising results in preclinical models and in patients. Here, we report for the first time the outcome of two infants with PROS having life-threatening conditions treated with alpelisib (25 mg) and monitored with pharmacokinetics. Patient 1 was an 8-mo-old girl with voluminous vascular malformation. Patient 2 was a 9-mo-old boy presenting with asymmetrical body overgrowth and right hemimegalencephaly with West syndrome. After 12 mo of follow-up, alpelisib treatment was associated with improvement in signs and symptoms, morphological lesions and vascular anomalies in the two patients. No adverse events were reported during the study. In this case series, pharmacological inhibition of PIK3CA with low-dose alpelisib was feasible and associated with clinical improvements, including a smaller size of associated complex tissue malformations and good tolerability.
Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib
Disclosures: F. Dubos reported personal fees from Sanofi-Pasteur, MSD, and Takeda outside the submitted work. T.K. Han reported being an employee at Novartis. F. Branle reported "other" from Novartis.Pharma.AG during the conduct of the study; and is a full-time employee of Novartis.Pharma AG Switzerland. A patent application (“BYL719 [alpelisib] for use in the treatment of PIK3CA-related overgrowth spectrum”; #WO2017140828A1) has been filed by Institut National de la Santé et de la Recherche Médicale, Centre National De La Recherche Scientifique, Université Paris Descartes, and Assistance Publique-Hôpitaux De Paris for the use of BYL719 (alpelisib) in the treatment of PIK3CA-related overgrowth spectrum (PROS/CLOVES syndrome). G. Canaud is the inventor. G. Canaud receives or has received consulting fees from Novartis, Vaderis, Fresenius Medical Care, Alkermes, IPSEN, and BridgeBio. No other disclosures were reported.
- Award Id(s): 101000948
- Award Id(s): ANR-18-RHUS-005
- Award Id(s): 19-CE14-0030-01
- Award Id(s): FDM202006011222
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Gabriel Morin, Caroline Degrugillier-Chopinet, Marie Vincent, Antoine Fraissenon, Hélène Aubert, Célia Chapelle, Clément Hoguin, François Dubos, Benoit Catteau, Florence Petit, Aurélie Mezel, Olivia Domanski, Guillaume Herbreteau, Marie Alesandrini, Nathalie Boddaert, Nathalie Boutry, Christine Broissand, Tianxiang Kevin Han, Fabrice Branle, Sabine Sarnacki, Thomas Blanc, Laurent Guibaud, Guillaume Canaud; Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib. J Exp Med 7 March 2022; 219 (3): e20212148. doi: https://doi.org/10.1084/jem.20212148
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