Response to Alpelisib in Clinically Distinct Pediatric Patients With PIK3CA-related Disorders

Abstract

PIK3CA-related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA-driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.

Four‐month‐old with severe PIK3CA‐related overgrowth spectrum disorder successfully treated with alpelisb

“…7,8 Consequently, hyperglycemia is a common adverse event of alpelisib in adults, 9,10 but less frequent in children possibly due to increased insulin sensitivity in this age group. 6,[10][11][12][13][14] Likewise, alpelisib could correct growth delay but could also stagnate linear growth. 6,13 In our patient, we measured IGF-1 after the initiation of alpelisib and, despite normal levels, her growth curve remained at À2 SD; therefore alpelisib induced growth delay could not be ruled out.…”

Facial infiltrating lipomatosis with hemimegalencephaly and lymphatic malformations caused by nonhotspot phosphatidylinositol 3‐kinase catalytic subunit alpha mutation

“…Alpelisib has better efficacy than sirolimus in reducing LM caused by PIK3CA variants 19 . In addition, alpelisib also had a preventive and reversing effect on adipose overgrowth located in other areas of the body 20,21 . The latest conclusions showed that significant volume reduction of facial soft tissues can be seen after the administration of alpelisib for 1 month, and continuous use can achieve the outcomes of volume reduction of fat and LM, sebaceous nevus hypopigmentation, improvement of oral, and speech function, the drug is ineffective for skeletal deformities 22 .…”

“…19 In addition, alpelisib also had a preventive and reversing effect on adipose overgrowth located in other areas of the body. 20,21 The latest conclusions showed that significant volume reduction of facial soft tissues can be seen after the administration of alpelisib for 1 month, and continuous use can achieve the outcomes of volume reduction of fat and LM, sebaceous nevus hypopigmentation, improvement of oral, and speech function, the drug is ineffective for skeletal deformities. 22 Targeted drugs offer new possibilities for the treatment of FIL: reducing soft tissue volume and infiltration through oral drugs, and then adjusting soft tissue and bone deformities together with surgery.…”

Congenital Vascular Malformations in Children: From Historical Perspective to a Multidisciplinary Approach in the Modern Era—A Comprehensive Review

“…Currently, alpelisib-a selective PI3Kα inhibitor-is being investigated and used in an experimental setting for patients with a PIK3CA or TEK mutation [83,84]. Another example is trametinib, which is a MEK inhibitor, and promising results have been reported in patients with complex lymphatic anomalies associated with mutations in the RASpathway [85].…”