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

Purpose: PIK3CA-related overgrowth spectrum (PROS) encompasses several rare conditions resulting from activating variants in PIK3CA. Alpelisib, a PI3K alpha-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 PI3K alpha as a valid therapeutic target for PROS symptom management.

Automated summary

EPIK-P1 study provides real-world evidence supporting the effectiveness and safety of alpelisib in patients with PROS. The study shows that alpelisib can effectively reduce lesion volume and provide additional clinical benefits in PROS patients. Adverse events were observed in a significant proportion of patients, but no deaths occurred.