BYL719 (alpelisib) for use in the treatment of PIK3CA-related overgrowth spectrum (pros-CLOVES syndrome)

A method of treating a plurality of symptoms of a PIK3CA-related overgrowth spectrum (PROS) disorder in an adult, child or infant suffering from a PROS disorder, comprising the steps of

• identifying an adult, child or infant suffering from a PROS disorder causing the plurality of symptoms due to overgrowth of multiple organs or tissues,
• administering orally to the subject with a therapeutically effective amount of BYL719 in the range of 15 to 500 mg or in the range of 0.3 to 12 mg/kg, and
• reversing the plurality of symptoms due to overgrowth of multiple organs or tissues, wherein the plurality of symptoms are selected from the group consisting of paraplegia, loss of bladder control, edema, enlarged circumference of thorax and abdomen, venous dilation, vascular tumors, elevated brain natriuretic peptide blood level, proteinuria, kidney dysfunction, cardiac enlargement, cardiac dysfunction, overgrown tissue, limb hypertrophy, dysregulated adipose tissue, scoliosis, enlarged bony structures without progressive bony overgrowth, benign tumors, megalencephaly-capillary malformation, lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, epidermal nevi, lymphatic malformation, muscle hypertrophy, kidney dysfunction, liver steatosis and spleen disorganization, and wherein the PROS disorder is selected from the group consisting of
• fibroadipose overgrowth;
• megalencephaly-capillary malformation syndrome;
• congenital lipomatous asymmetric overgrowth, lymphatic capillary, venous and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies and/or scoliosis (CLOVES) syndrome;
• hemihyperplasia multiple lipomatosis;
• and
• Klippel-Trenaunay syndrome, and
• wherein said PROS disorder is not responsive to treatment with rapamycin.

A method of treating a patient who is an adult having a PIK3CA-related overgrowth spectrum (PROS) disorder caused by a somatic mosaic mutation, comprising the steps of

• identifying the subject as suffering from the PROS disorder of an overgrowth of multiple organs or tissues;
• administering orally to the subject a therapeutically effective amount of BYL719, wherein the therapeutically effective amount of BYL719 is a starting dose of 250 mg daily;
• and
• reversing the overgrowth of multiple organs or tissues;
• wherein said PROS disorder is not responsive to treatment with rapamycin.

A method of treating a patient who is a child having a PIK3CA-related overgrowth spectrum (PROS) disorder caused by a somatic mosaic mutation, comprising the steps of

• identifying the subject as suffering from the PROS disorder of an overgrowth of multiple organs or tissues;
• administering orally to the subject a therapeutically effective amount of BYL719, wherein the therapeutically effective amount of BYL719 is a starting dose of 50 mg daily;
• and
• reversing the overgrowth of multiple organs or tissues;
• wherein said PROS disorder is not responsive to treatment with rapamycin.