Health-Related Quality of Life and Symptom Severity Among Patients With PIK3CA-Related Overgrowth Spectrum: A Mixed-Methods Study to Understand Real-World Experience With Alpelisib Treatment.

PIK3CA-related overgrowth spectrum (PROS) includes several rare overgrowth disorders resulting from somatic gain-of-function mutations in PIK3CA. Despite treatment advances, including the recent approval of alpelisib for PROS in the United States, literature detailing the patient experience with PROS is limited. This observational study (NCT05294289) evaluated health-related quality of life (HRQoL) and symptom burden among patients with PROS in the United States. Patients and caregivers of patients with PROS were recruited via patient advocacy organizations and clinical sites and stratified by alpelisib treatment status. Quantitative data were collected for up to 12 months through online surveys. Qualitative interviews were conducted at the time of study enrollment for a subset of participants receiving alpelisib. Among the 77 enrolled participants, representing 6 syndrome types, 19 were caregivers. Fourteen participants reported alpelisib treatment at enrollment. Median patient age was 26 years; median time since PROS diagnosis was 7 years. During the study, participants reported a negative impact of PROS on HRQoL, most often related to pain and loss of physical functioning. Negative effects were found to persist over the entire study period. Participants receiving alpelisib self- and proxy-reported improvements in pain, physical functioning, and daily activities in both qualitative interviews and quantitative surveys. Additional research is warranted to better understand the natural history of PROS and assess the real-world impact of therapeutic treatment options, such as alpelisib.