The Food and Drug Administration (FDA) has approved alpelisib (Piqray) to treat postmenopausal women or men who have hormone receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutated, advanced or metastatic breast cancer that has progressed during or after endocrine-based (also known as antihormonal) therapy. Alpelisib should be coadministered with the endocrine therapy fulvestrant (Faslodex).

To confirm that a patient has advanced or metastatic breast cancer related to a mutated PIK3CA gene, a specific genetic test must be conducted. The FDA has also approved a companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, for this purpose.

Although there are no black box warnings for alpelisib, the drug's labeling carries several warnings and precautions, including the risk of severe hypersensitivity, severe cutaneous reactions (including Stevens-Johnson syndrome and erythema multiforme), severe hyperglycemia (including ketoacidosis), severe pneumonitis, severe diarrhea (including dehydration and acute kidney injury), and embryo-fetal toxicity. The most common adverse effects (seen in 20% or more of patients) include altered glucose levels (more commonly elevated glucose, but decreased glucose is also possible), diarrhea, rash, decreased lymphocyte count, increased gamma-glutamyl transferase levels, nausea, increased alanine aminotransferase levels, fatigue, decreased hemoglobin, increased lipase, loss of appetite, stomatitis, vomiting, weight loss, lowered calcium, prolonged activated partial thromboplastin time, and alopecia.

Nurses and NPs caring for patients receiving alpelisib should be alert for any of these serious adverse effects. If the patient exhibits severe hypersensitivity (dyspnea, flushing, rash, fever, tachycardia), alpelisib should be stopped permanently. For patients with signs and symptoms of severe skin reactions (rash with blistering, peeling skin), the drug should be stopped until the etiology of the reaction is confirmed. If a patient is found to have Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis, the drug should be permanently discontinued. Alpelisib's labeling contains specifics regarding dose modifications for adverse reactions. If the patient begins to exhibit hyperglycemia, antihyperglycemic medications may be indicated or the alpelisib dosage may need adjustment. Depending on the severity of the hyperglycemic reactions, alpelisib may be stopped temporarily, the dosage reduced, or the drug discontinued. To identify pneumonitis, the nurse or NP should assess patients carefully for respiratory changes, clinical symptoms, or radiologic changes. Alpelisib should be withheld temporarily or possibly stopped permanently if severe pneumonitis develops. Although most patients will have some diarrhea, the nurse or NP should be vigilant for severe cases. These patients will need rehydration and antidiarrheal treatment. The dose of alpelisib should be interrupted, decreased, or discontinued depending on the diarrheal severity.

For complete prescribing information for alpelisib, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212526s000lbl.pdf.