Abstract 468P
Background
Efficacy and safety of alpelisib (ALP) in adult (≥18 y) and pediatric (2-17 y) patients (pts) with PROS was demonstrated in EPIK-P1. In the primary endpoint analysis, 37.5% of complete cases (12/32) showed ≥20% reduction in target lesion volume after 24 weeks (w) or 6 months. Here, we present the results of pre-specified secondary endpoints i.e. evaluation of clinical benefit in pediatric pts with PROS receiving ALP under compassionate use.
Methods
EPIK-P1 was a retrospective noninterventional chart review of pts ≥2 y with PROS experiencing severe/life-threatening conditions and initiated ALP treatment (pediatric, 50 mg/day) ≥24 w before data cutoff (9 Mar 2020). Secondary objectives assessed treatment effect on performance status (PS), frequency of PROS-related surgeries, and signs/symptoms over time in the full study population (N=57).
Results
There were 39 pediatric pts in EPIK-P1: 11, aged 2-5 y; 12, aged 6-11 y; and 16, aged 12-17 y. Date of ALP initiation was defined as the index date. Between a pt’s diagnosis and the pre-index period (24 w before index date), 33/39 pediatric pts (84.6%) underwent ≥1 surgery with a median of 4 (range, 1-15). Surgeries were reported in all age groups. In the 24 w before treatment, 4 pediatric pts (10.3%, 3 aged 2-5 y, 1 aged 12-17 y) had ≥1 PROS-related surgery. In the first 24 w of ALP treatment, no pediatric pts required surgery due to disease progression, 1 pt required surgery for another reason. Lipomatosis, scoliosis, hypertrophy, inflammation, and developmental delays were reported in ≥20% of pediatric pts at index date. Improvement in these signs/symptoms was seen as early as 12 w. Resolution was reported in some cases by the end of the study. Improvement in PS score (ECOG, Lansky, Karnofsky) at 24 w was seen in 8 (24.2%) pediatric pts.
Conclusions
A decrease in PROS-related surgeries and improvement in both performance status and PROS-related signs/symptoms were observed in pediatric pts from the EPIK-P1 study. Along with previously reported lesion volume reduction and well-tolerated safety profile, these real-world data provide evidence that ALP provides meaningful clinical benefit to pediatric pts with PROS.
Clinical trial identification
NCT04285723.
Editorial acknowledgement
We thank Avinash Yerramsetti, MPharm. of Novartis Healthcare Pvt Ltd (Hyderabad, India) for providing medical editorial assistance in accordance with the Good Publication Practice (GPP3) guidelines for the preparation of this abstract.
Legal entity responsible for the study
Novartis Pharmaceutical Corporation.
Funding
Novartis Pharmaceutical Corporation.
Disclosure
G. Canaud: Financial Interests, Personal, Other, Consulting fee: Novartis Pharmaceuticals, BridgeBio, Fresenius Medical Care; Financial Interests, Personal, Proprietary Information, WO2017140828A1: Patent application. A. Irvine: Financial Interests, Personal, Other, Consulting fee: AbbVie, Arena Pharmaceuticals, Benevolent AI, Chugai, Dermavant; Financial Interests, Personal, Speaker’s Bureau: AbbVie, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi. D.M. Adams: Financial Interests, Other, Consulting fee: Novartis Pharmaceuticals. N.O. Ankrah: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Novartis Pharmaceuticals. P. O’Connell: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Novartis Pharmaceuticals. J.C. López Gutiérrez: Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre Pharmaceuticals; Financial Interests, Personal, Other, Travel support: Pierre Fabre Pharmaceuticals.