Summary of Clinical Use

Multiple clinical trials are assessing alpelisib in a range of PIK3CA mutated solid and haematologic cancers, either as a monotherapy or in combination with established and/or novel oncology drugs. Click here to link to ClinicalTrials.gov's full list of alpelisib trials. A combination therapy of alpelisib and fulvestrant was FDA approved in May 2019 [4], as a treatment for men and postmenopausal women with HR+ve, HER2-ve, PIK3CA-mutated advanced/metastatic breast cancer that has progressed on or after an endocrine-based therapy. CLOVES syndrome is a genetic disorder that results from gain-of-function mutations of the PIK3CA gene (e.g. the H1047R mutation), and is one of a spectrum of PIK3CA-related overgrowth syndromes (PROS). A study in France demonstrated that targeted therapy with alpelisib produced substantial therapeutic effects in all nineteen CLOVES patients included in the trial [5]. The EMA granted orphan designation as a PROS therapy in March 2021. In April 2022, the FDA approved alpelisib (Vijoice) as the first therapy for patients (≥2 years old) with severe manifestations of PROS. A case study in a child with congenital hyperinsulinism (due to homozygous deletion of ABCC8) found that adjuvant alpelisib improved glucose control without serious adverse effects, and deferred the necessity for total pancreatectomy [1].

Mechanism Of Action and Pharmacodynamic Effects

Alpelisib selectively inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This results in inhibition of tumour cell growth and survival in susceptible tumour cell populations.