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. 2023 Dec;25(12):100969.
doi: 10.1016/j.gim.2023.100969. Epub 2023 Aug 24.

Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS)

Guillaume Canaud  1 , Juan Carlos Lopez Gutierrez  2 , Alan D Irvine  3 , Pierre Vabres  4 , Jordan R Hansford  5 , Nii Ankrah  6 , Fabrice Branle  7 , Athanasia Papadimitriou  7 , Antonia Ridolfi  8 , Paul O'Connell  9 , Stuart Turner  10 , Denise M Adams  11
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Free article

Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS)

Guillaume Canaud et al. Genet Med. 2023 Dec.
Free article

Abstract

Purpose: PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions resulting from activating variants in PIK3CA. Alpelisib, a PI3Kα-selective inhibitor, targets the underlying etiology of PROS, offering a novel therapeutic approach to current management strategies. This study evaluated the safety and efficacy of alpelisib in pediatric and adult patients with PROS.

Methods: EPIK-P1 (NCT04285723) was a non-interventional, retrospective chart review of 57 patients with PROS (≥2 years) treated with alpelisib through compassionate use. Patients had severe/life-threatening PROS-related conditions and confirmed PIK3CA pathogenic variant. The primary end point assessed patient response to treatment at Week 24 (6 months).

Results: Twenty-four weeks (6 months) after treatment initiation, 12 of 32 (37.5%) patients with complete case records included in the analysis of the primary end point experienced a ≥20% reduction in target lesion(s) volume. Additional clinical benefit independent from lesion volume reduction was observed across the full study population. Adverse events (AEs) and treatment-related AEs were experienced by 82.5% (47/57) and 38.6% (22/57) of patients, respectively; the most common treatment-related AEs were hyperglycemia (12.3%) and aphthous ulcer (10.5%). No deaths occurred.

Conclusion: EPIK-P1 provides real-world evidence of alpelisib effectiveness and safety in patients with PROS and confirms PI3Kα as a valid therapeutic target for PROS symptom management.

Keywords: Alpelisib; Overgrowth; PIK3CA; PROS.

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Conflict of interest statement

Conflict of Interest Guillaume Canaud reports consulting fees from Novartis, BridgeBio, Fresenius Medical Care, Alkernes, and Vaderis; support for attending meetings and/or travel from Novartis; patent with Novartis (WO2017140828A1); and participation on data safety/advisory board for Novartis. Juan Carlos Lopez Gutierrez reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pierre Fabre Pharmaceuticals and support for attending meetings and/or travel from Pierre Fabre Pharmaceuticals. Alan D. Irvine reports consulting fees from Sanofi, Regeneron, Novartis, AbbVie, Menlo, Leo Pharma, Eli Lilly, Dermavant, Benevolent AI, Pfizer, and Almirall; speaker fees from Leo Pharma, Regeneron, Sanofi, Eli Lilly, and AbbVie; royalties from UpToDate; participation on data safety/advisory board for Novartis and OM Pharma; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for International Eczema Council (Director- unpaid). Pierre Vabres reports honoraria from Novartis. Jordan R. Hansford reports consulting fees from Bayer Pharmaceuticals Australia, Alexion Pharmaceuticals, and Boxer Capital; payment for expert testimony from Bayer Pharmaceuticals Australia; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for ANZCHOG (Director). Nii Ankrah reports being an employee of Novartis and stock ownership in Novartis. Fabrice Branle reports being an employee of Novartis Pharma AG Switzerland and stock ownership in Novartis. Athanasia Papadimitriou reports being an employee of Novartis Pharma AG Switzerland and stock ownership in Novartis. Antonia Ridolfi reports being an employee of Novartis. Paul O’Connell reports being an employee of Novartis and stock ownership in Novartis. Stuart Turner reports being an employee of Novartis and stock ownership in Novartis. Denise M. Adams reports consulting fees from Novartis and Venthera; royalties from UpToDate; and participation on data safety/advisory board for Novartis.

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