P4.A007: HRQoL, Symptom Severity, and Pain Among Patients Treated with Alpelisib for PROS

Background: PIK3CA-related overgrowth spectrum (PROS) includes several phenotypically different rare overgrowth disorders driven by somatic gain-of-function mutations in PIK3CA. Patients with PROS experience complications, such as pain and functional impairment, that can be debilitating and lead to early morbidity and even mortality, with few treatment options available. Alpelisib, a PI3Kα inhibitor, addresses the underlying cause of PROS and was granted accelerated approval by the US Food and Drug Administration for treatment of adult and pediatric patients with severe manifestations of PROS who require systemic therapy. The objective of this analysis was to evaluate health-related quality of life (HRQoL), symptom severity, and pain among patients receiving treatment with alpelisib for PROS.

Methods: This US-based, mixed-methods, observational study collected data through interviews and web-based longitudinal surveys. Participants were recruited with the support of patient advocacy organizations and clinical sites. Outcomes for the first survey are presented for standardized measures, bespoke survey items, and interview transcripts coded using a thematic analysis approach. The study is registered on ClinicalTrials.gov (NCT05294289).

Results: Fourteen participants (8 caregivers, 5 adults, 1 adolescent), representing 6 syndrome types, were enrolled and completed the first online survey. Mean patient age was 16.9 years (range: 5-39), mean time since PROS diagnosis was 10.1 years, and mean time since initiation of alpelisib was 9.1 months (range: 0-28).

Most participants (71%) reported better health (both physical and general) at the time of the first online survey than prior to initiation of alpelisib, with 57% indicating PROS symptoms were either mild or absent. The sample had a mean PROMIS pain score of 2.2 (range: 0-4, pain rated on a 0-10 numeric scale). Compared with the general population, the largest deficits were seen in the PROMIS physical functioning domain.

Ten one-on-one, 60-minute interviews were conducted. Participants described improvements in pain and overgrowth, linking them to treatment with alpelisib. Participants also verbally described the improvements in functional impairments including physical functioning, emotional wellbeing, activities of daily living, and work or school since initiating alpelisib.

Conclusion: Participants reported improvements in HRQoL, symptom severity, and pain after initiating treatment with alpelisib. This real-world study provides important information from patients with PROS treated with alpelisib and their caregivers, including reported improvements in pain and functioning. These data complement those from EPIK-P1 (NCT04285723), wherein alpelisib demonstrated effectiveness and safety for the treatment of PROS, further supporting the clinical benefit of alpelisib for patients. Ongoing data collection efforts in patients with PROS not treated with alpelisib will provide additional context for this work.