Alpelisib treated a rare disease in infants causing tissue overgrowth

A recent case report described the successful treatment of 2 young infants with a PIK3CA-related proliferative spectrum using the breast cancer drug alpelisib.

PIK3CA-the overgrowth-related overgrowth spectrum (PROS) is a group of rare and incurable diseases caused by mutations in the PIK3CA gene that leads to the malformation and proliferation of various parts of the body.

A recent case report in the Journal of Experimental Medicine (YWAM) describes the successful treatment of 2 young infants with PROS using the breast cancer drug alpelisib.

PROS encompasses a group of diseases which, taken together, are thought to affect approximately 1 in 70,000 people. Mutations in the PIK3CA gene impairs cell growth and proliferation, causing malformation or overgrowth of various tissues, including the brain, blood vessels, muscles, and bones, often resulting in severe disability and premature death.

Although some symptoms of PROS can be alleviated with surgery and other forms of palliative care, there are currently no approved medical treatments to treat the condition. However, alpelisib, a PIK3CA inhibitor recently approved to treat some forms of breast cancer, has shown promising results both in animal models of PROS and in a small number of adult and older pediatric patients. The drug is currently being studied in a series of larger clinical trials, but, until now, there were no data on the effectiveness of alpelisib in young infants with PROS.

A team of researchers has identified 2 young patients – an 8-month-old girl and a 9-month-old boy – with a variety of severe symptoms caused by mutations in the PIK3CA uncomfortable. These symptoms included extreme blood vessel malformations and asymmetric proliferation of limbs and fingers, and, in the boy’s case, enlargement of the right hemisphere of the brain associated with epileptic spasms.

Daily oral doses of 25 mg of alpelisib produced rapid and significant clinical improvement in all of these symptoms. In the case of the girl, for example, 12 months of treatment with alpelisib reduced the number of vascular malformations and significantly reduced the size of her right leg, allowing her to stand and walk with help, while the boy’s epileptic spasms were greatly reduced.

The overall development of the children appeared to be significantly improved and neither patient experienced adverse effects from alpelisib treatment. Further analyzes revealed that at a daily dose of 25 mg, levels of alpelisib accumulated in children’s blood were well below levels that can be safely tolerated by adults.

“Given the well-established safety profile of alpelisib at the approved dose of 300 mg in adults, these low exposures support continued treatment with 25 mg of alpelisib in these young patients with PROS,” said Guillaume Canaud, MD, PhD, Necker-Enfants Hospital for the Sick, AP-HP; Paris Descartes University, Inserm, in a report. “The results of alpelisib treatment in these two infants are encouraging, but they should be interpreted with caution and will need to be confirmed by future studies.”


Morin G, Degrugillier-Chopinet C, Vincent M, et al. Treatment of two infants with PIK3CA-related proliferative spectrum with alpelisib. J. Exp. Med. Published online January 26, 2022. doi:10.1084/jem.20212148?PR

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