FDA approved Piqray (alpelisib) for PIK3CA-Mutated HR-Positive, HER2-Negative Advanced Breast CancerFDA approved New Targeted Drug for a Common Type of Advanced Breast Cancer

Alpelisib is a kinase inhibitor. It inhibits phosphatidylinositol-3-kinase (PI3K) with activity against the alpha isoform. The exact mechanism of action in HR-positive, HER2-negative breast cancer with PIK3CA mutations is not fully elucidated in the label.

Piqray is indicated in combination with fulvestrant for the treatment of adults 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. Patient selection requires the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens. If no mutation is detected in a plasma specimen, tumor tissue should be tested.

The recommended dose of Piqray is 300 mg (two 150 mg tablets) taken orally once daily with food. Continue treatment until disease progression or unacceptable toxicity. Patients should take the dose at approximately the same time each day. Swallow tablets whole; do not chew, crush, or split. If a dose is missed, it can be taken with food within 9 hours after the usual time. After more than 9 hours, skip the dose for that day. If vomiting occurs after taking the dose, do not take an additional dose that day; resume the next day at the usual time. When given with Piqray, the recommended dose of fulvestrant is 500 mg on Days 1, 15, and 29, and once monthly thereafter. Dose modifications for adverse reactions include dose interruption, reduction, or discontinuation. The starting dose is 300 mg once daily; first dose reduction is 250 mg once daily (one 200 mg tablet and one 50 mg tablet); second dose reduction is 200 mg once daily (one 200 mg tablet). If further dose reduction below 200 mg once daily is required, discontinue Piqray. Only one dose reduction is permitted for pancreatitis.

The approval is based on the SOLAR-1 trial, a randomized, double-blind, placebo-controlled study. Trial data not available in label.

The label includes warnings and precautions for severe cutaneous adverse reactions (SCARs), hyperglycemia, diarrhea, and pneumonitis. If a SCAR is confirmed, permanently discontinue Piqray; do not reintroduce. For rash, dose modifications are recommended based on grade. Before initiating treatment, test fasting plasma glucose (FPG) and HbA1c, and optimize blood glucose. Consider premedication with metformin based on patient risk factors. After initiating, monitor fasting glucose at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months. Contraindications: Not reported in label.

Piqray is a targeted therapy for patients with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer after progression on endocrine therapy. It is used in combination with fulvestrant. Patient selection requires confirmation of PIK3CA mutation status.