FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum.

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• PIK3CA-related overgrowth spectrum (PROS) involves complex overgrowth.
• Systemic therapy is crucial for severe PROS manifestations.

Purpose of the Study:

• To evaluate the efficacy of alpelisib in patients with severe PROS.
• To assess radiologic and clinical benefits of alpelisib treatment.

Main Methods:

• Real-world data (RWD) from the single-arm EPIK-P1 study (NCT04285723).
• Volumetric-based criteria used for radiologic response assessment at week 24.
• Confirmed radiologic response defined as ≥20% reduction in lesion volume.

Main Results:

• 27% of patients (n=37) achieved radiologic response at week 24.
• 60% of responders demonstrated a duration of response (DOR) of ≥12 months.
• Early clinical benefit signals, including symptom improvement, were observed.

Conclusions:

• Alpelisib demonstrates efficacy in treating severe PROS, supported by RWD.
• The drug offers a new therapeutic option for PROS patients requiring systemic therapy.
• Further research may explore long-term outcomes and broader clinical applications.