468P Clinical benefit of alpelisib in pediatric patients with PIK3CA-related overgrowth spectrum (PROS): An EPIK-P1 analysis

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. 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). 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. 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.