LBA23 - EPIK-P1: Retrospective chart review study of patients (pts) with <italic>PIK3CA</italic>-related Overgrowth Spectrum (PROS) who have received alpelisib (ALP) as part of a compassionate use programme

Background

PROS is a group of rare, heterogeneous disorders resulting from activating somatic mutations in the PIK3CA gene. No medical treatment (tx) is approved for PROS. ALP, a PI3Kα inhibitor targeting the driver of PROS, showed promising results in pts (n=19) with PROS (Venot Nature 2018).

Methods

EPIK-P1 is a retrospective non-interventional medical chart review of pts (age ≥2 years) with PROS treated with ALP. Pts had a diagnosis of PROS, severe or life-threatening conditions, confirmed PIK3CA mutation, and received ≥1 dose of ALP (adult, 250 mg/d; paediatric, 50 mg/d) ≥24 weeks before the cutoff date (9 MAR 2020). Primary objective was to assess efficacy by the proportion of responders (pts with ≥20% reduction from tx start in the sum of target lesion volume) at week 24 by independent central review. Secondary objectives included assessing ALP safety and clinical benefit.

Results

Data were abstracted from 57 pts (39 paediatric, 18 adult) at 7 sites in 5 countries. Median length of exposure (start of tx to last tx per cutoff date) was 18.1 mo. In the primary endpoint analysis at week 24, 37.5% (95% CI, 21.1-56.3%) of pts (12/32 of the complete cases) responded; sensitivity analysis showed similar results. Of the 12 responders, none experienced disease progression or death by data cutoff. 23 out of 31 pts (74.2%) reported reduction in sum of target lesion volume with mean reduction of 13.7%. At week 24, proportion of pts with improvement in the most frequent (in the full-study population) PROS-related symptoms/signs was pain 90.9% (20/22), fatigue 76.2% (32/42), vascular malformation 78.9% (30/38), limb asymmetry 69.0% (20/29), and disseminated intravascular coagulation 55.2% (16/29). In the first 24 weeks, there were no surgeries due to disease progression. Adverse events (AEs) and tx-related AEs were experienced by 82.5% (n=47) and 38.6% (n=22) of pts, respectively; no deaths were reported. The most common tx-related AEs were hyperglycaemia (n=7, 12.3%), aphthous ulcer (n=6, 10.5%), and stomatitis (n=3, 5.3%).

Conclusions

The real-world evidence from the EPIK-P1 study demonstrates that ALP confers clinically meaningful efficacy to, and is well tolerated in, pts with PROS.

Clinical trial identification

NCT04285723.

Editorial acknowledgement

We thank Rob Camp, PhD, and Kymberleigh Romano, PhD, of Healthcare Consultancy Group, LLC, for their medical editorial assistance with this abstract, which was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

G. Canaud: Financial Interests, Personal, Other, Consulting fees & Travel support: Novartis Pharmaceuticals Corporation; Financial Interests, Personal, Other, Consulting fees: Bridgebio; Other, Personal and Institutional, Other, Patent pending WO2017140828A1: Hôpital Necker, Université de Paris; Financial Interests, Personal, Other, Consulting fees: Fresenius Medical Care. J.C. López Gutiérrez: Financial Interests, Personal, Speaker’s Bureau, Travel support and speakers' bureau fees: Pierre Fabre Pharmaceuticals. A. Irvine: Financial Interests, Personal, Speaker’s Bureau, Consulting fees: AbbVie; Financial Interests, Personal, Other, Consulting fees: Arena Pharmaceuticals; Financial Interests, Personal, Other, Consulting fees: Benevolent AI; Financial Interests, Personal, Other, Consulting fees: Chugai; Financial Interests, Personal, Other, Consulting fees: Dermavant; Financial Interests, Personal, Other, Consulting fees: Genentech; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: LEO Pharma; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Lilly; Financial Interests, Personal, Other, Consulting fees: Menlo Therapeutics; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Novartis; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Pfizer; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Regeneron; Financial Interests, Personal, Speaker’s Bureau, Consulting fees: Sanofi; Financial Interests, Personal, Other, Consulting fees: UCB. N. Ankrah: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals Corporation. A. Papadimitriou: Financial Interests, Personal, Full or part-time Employment: Novartis Pharmaceuticals Corporation. A. Ridolfi: Financial Interests, Personal, Full or part-time Employment: Novartis Pharma S.A.S. D.M. Adams: Financial Interests, Personal, Other, Consulting fees: Novartis Pharmaceuticals Corporation; Financial Interests, Personal, Other, Consulting fees: Venthera.