Alpelisib ‘Efficacious’ For PIK3CA-Related Overgrowth Spectrum

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Patients with PIK3CA-related overgrowth spectrum (PROS) benefit from treatment with alpelisib, indicate findings from the EPIK-P1 chart review of adults and children given the PI3K inhibitor as part of a compassionate use programme. 

Presenting the results at the ESMO Congress 2021, Guillaume Canaud, from the University of Paris in France, explained that PROS is a rare, phenotypically variable group of disorders associated with sporadic somatic gain-of-function mutations in the PI3KCA gene, and estimated to occur in around 14 people per million. 

PROS complications include haemorrhage and embolisms, vascular and lymphatic anomalies, congenital neurological complications and development delays, skeletal and organ abnormalities, and superficial infections, he said. 

The 57 patients included in EPIK-P1 were from five countries and all were aged 2 years or older with PROS and a confirmed PIK3CA mutation. The patients were given one or more doses of alpelisib to manage a severe or life-threatening complication between September 2019 and March 2020. 

The median age of the 39 paediatric patients was 10.0 years and the median age of the 18 adults was 25.5 years. The majority of patients had congenital onset of disease and a mosaic distribution overgrowth type. 

The primary endpoint of a 20% or greater reduction in target lesion volume was selected for being the “commonly accepted threshold in vascular anomalies” and for its “association with a clinical benefit in PROS”, explained Guillaume Canaud. 

The primary endpoint was met in 37.5% of 32 patients with a suitable target lesion and imaging available. Furthermore, 74.2% of the 31 patients with imaging at baseline and week 24 achieved a reduction in target lesion volume, with an average reduction of 13.7%. 

None of the patients experienced disease progression or died during the study period, the investigator emphasized. 

Assessment of PROS-related signs and symptoms – such as fatigue, vascular malformation, disseminated intravascular coagulation, limb asymmetry and pain – revealed “clinically meaningful improvement” that led to better patient health status and function, the presenter commented. 

“Reduction in the number of grade 3/4 events were observed as early as week 12, confirmed at week 24, and were sustained and/or improved over time”, he said. 

And while disease-related surgery was common in the years before alpelisib initiation, there were no such procedures required in the 24 weeks after treatment. 

Guillaume Canaud reported that alpelisib was given at a median dose of 50 mg/day in children and 250 mg/day in adults for a median of 18 months and that treatment-related adverse events (AEs) occurred less frequently in children than adults.  

The most common AEs were diarrhoea (15.8%), hyperglycaemia (12.3%) and aphthous ulcers (10.5%), with all cases of the latter two symptoms considered to be treatment-related. Cellulitis was the most common grade 3–4 event (3.5%), with one adult case considered treatment-related. 

“AEs were mild in severity, transient and manageable with appropriate intervention”, the presenter summarised, adding that the safety profile “compares favourably to that of alpelisib in the oncology setting”. 

None of the patients discontinued alpelisib due to AEs and 91.2% of patients continued on treatment until the end of the study, he continued. 

Guillaume Canaud concluded: “Real-world data from EPIK-P1 demonstrate that alpelisib is an efficacious and safe novel therapeutic approach for patients with PROS”.  

Reference  

LBA23 - Canaud G, López Gutiérrez JC, Irvine A, et al. EPIK-P1: Retrospective chart review study of patients (pts) with PIK3CA-related overgrowth spectrum (PROS) who have received alpelisib (ALP) as part of a compassionate use programme. Ann Oncol 2021;32(suppl_5): S1283–S1346. doi: 10.1016/annonc/annonc741