General Information

Piqray (alpelisib)is a kinase inhibitor.

Piqray is specifically indicated for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Piqray is supplied as a tablet for oral administration. The recommended dose is 300 mg (two 150 mg tablets) taken orally once daily with food. For adverse reactions, consider dose interruption, dose reduction, or discontinuation. 

Mechanism of Action

Piqray (alpelisib) is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. Gain-of-function mutations in the gene encoding the catalytic α-subunit of PI3K (PIK3CA) lead to activation of PI3Kα and Akt-signaling, cellular transformation and the generation of tumors in in vitro and in vivo models. 

In breast cancer cell lines, alpelisib inhibited the phosphorylation of PI3K downstream targets, including Akt and showed activity in cell lines harboring a PIK3CA mutation. In vivo, alpelisib inhibited the PI3K/Akt signaling pathway and reduced tumor growth in xenograft models, including models of breast cancer. PI3K inhibition by alpelisib treatment has been shown to induce an increase in estrogen receptor (ER) transcription in breast cancer cells. The combination of alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA mutated breast cancer cell lines.

Side Effects

Adverse effects associated with the use of Piqray may include, but are not limited to, the following:

• glucose increased
• creatinine increased
• diarrhea
• rash
• lymphocyte count decreased
• GGT increased
• nausea
• ALT increased
• fatigue
• hemoglobin decreased
• lipase increased
• decreased appetite
• stomatitis
• vomiting
• weight decreased
• calcium decreased
• glucose decreased
• aPTT prolonged
• alopecia

Clinical Trial Results

The FDA approval of Piqray was based on SOLAR-1 trial, a randomized trial of 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed while on or after receiving an aromatase inhibitor. Patients received either Piqray (300 mg) or placebo orally once daily on a continuous basis, plus fulvestrant (500 mg) administered intramuscularly on Cycle 1, Days 1 and 15, and then on Day 1 of every 28-day cycle. Patients received treatment until radiographic disease progression or unacceptable toxicity. Tumor assessments were performed every 8 weeks for the first 18 months and every 12 weeks thereafter. Results from the trial showed the addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.