New Therapy Shows Promise For PIK3CA-Related Overgrowth Spectrum in Retrospective Study

Data has recently been announced from a study investigating the efficacy of a new therapy called Alpelisib, for the treatment of PIK3CA-related overgrowth spectrum (PROS). The study was called EPIK-P1.

Results from this study were recently presented at the 2021 European Society of Medical Oncology.


PROS was first developed in 2013 to describe a full group of conditions. All of these conditions are rare, and all are the result of a PIK3CA mutation. The PROS classification includes conditions such as CLOVES syndrome, KTS, ILM, FIL, HHML, FAVA, muscular HH, macrodactyly, MCAP/M-CM, FAO, seborrheic keratosis, benign lichenoid keratosis, CLAPO syndrome, as well as epidermal nevus.

These conditions all are overgrowth conditions which lead to anomalies within the blood vessels, the lymphatic system, and more. The overgrowth or malformation is typically located where the PIK3CA mutation is located. PROS often impact patient’s mobility as well as their cognitive function. The group of conditions can have life-threatening complications.

Unfortunately, there are currently no approved therapies for PROS. Each patient has a different care plan which may include surgery as well as radiologic embolization. But there is clearly a need for an approved, effective treatment for this patient population. The goal is not simply to address symptoms, but to find something that will treat the underlying cause.


This study was a retrospective and global study. It included pediatric and adult patients who were diagnosed with PROS and had been on the Alpelisib treatment. Each of these patients was taking the treatment as a part of the compassionate use program as it is not yet FDA approved.

Through a review of medical charts, researchers evaluated the efficacy of daily Alpelisib treatment.

The primary endpoint of this investigation was the proportion of all of the PROS patients who had achieved response by 24 weeks. Response was defined as a minimum of 20% reduction in the target lesion volume. This was assessed with central imaging.

There were a total of 57 patients in this investigation. Of these, just 18 were adults. The patients spanned seven trial sites in 5 different countries.

The results demonstrated that Alpelisib is able to reduce the volume of lesions, improve symptoms, and minimize signs of the condition in both pediatric patients and adult patients. 38% of all patients reached response. 74% had some reduction in their lesion volume. Further, not a single patient experienced disease progression. There were also documented improvements in pain, vascular malformation, intravascular coagulation, limb asymmetry, and fatigue.

The most common adverse events were stomatitis, diarrhea, hyperglycemia, and alpthous ulcers. The most common grade 3/4 AE was cellulitis. Most of the AEs were mild-moderate. Additionally, no AE was so serious that anyone discontinued treatment.

Alpelisib already has been granted Breakthrough Therapy Designation. Patients are hopeful it could be approved soon.

You can read more about this therapy and PROS here.

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