Alpelisib

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-authorized test following progression on or after an endocrine-based regimen. PIQRAY is a kinase inhibitor 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-authorized test following progression on or after an endocrine-based regimen.

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.

Recommended Dosage: 300 mg orally once daily with food. For adverse reactions, consider dose interruption, dose reduction, or discontinuation.

PIQRAY is contraindicated in patients with severe hypersensitivity to it or any of its components. Severe hypersensitivity to PIQRAY or to any of its components.

Severe Hypersensitivity: Permanently discontinue PIQRAY. Promptly initiate appropriate treatment. Severe Cutaneous Adverse Reactions (SCARs): PIQRAY can cause SCARs, including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Interrupt PIQRAY for signs or symptoms of SCARs. Permanently discontinue PIQRAY if SCARs are confirmed. Hyperglycemia: PIQRAY can cause severe hyperglycemia, in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS) or ketoacidosis. Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. Consider premedication with metformin prior to the initiation of PIQRAY based on patient risk factors for hyperglycemia, gastrointestinal tolerability, and clinical situation.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Severe Hypersensitivity Severe Cutaneous Adverse Reactions Hyperglycemia Pneumonitis Diarrhea or Colitis Most common adverse reactions, including laboratory abnormalities (all Grades, incidence ≥ 20%) were increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma-glutamyl transferase (GGT), nausea, increased alanine aminotransferase (ALT), fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time (aPTT), and alopecia.

Strong CYP3A Inducers: Avoid coadministration. Consider an alternative concomitant drug with no or minimal potential to induce CYP3A. BCRP Inhibitors: Avoid coadministration. If unable to use alternative drugs, closely monitor for increased adverse reactions.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).