FDA Approves First PI3K Inhibitor for Breast Cancer

The U.S. Food and Drug Administration (FDA) approved Piqray® (alpelisib) tablets for use in combination with the endocrine therapy fulvestrant to treat postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer following disease progression on or after an endocrine-based regimen. This is the first PI3K inhibitor approved for the treatment of breast cancer.

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or liquid biopsy. Patients who screen negative with the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

Improved survival with alpelisib and fulvestrant combo

The FDA decision was based on results of the randomized SOLAR-1 trial that included 572 postmenopausal women and men with relapsed/refractory HR-positive, HER2-negative, advanced or metastatic breast cancer following treatment with an aromatase inhibitor. The study found that the addition of alpelisib to fulvestrant significantly prolonged progression-free survival (median = 11 months vs. 5.7 months) in patients with PIK3CA-mutated tumors.

The most common adverse events associated with alpelisib are hyperglycemia, increased creatinine, diarrhea, rash, decreased serum lymphocyte count, elevated liver enzymes, nausea, fatigue, low red blood cell count, increased lipase, decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolongation, and hair loss.


Healthcare professionals should monitor patients taking alpelisib for severe hypersensitivity reactions. Patients should be aware of potentially severe skin reactions, and physicians are advised not to initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson Syndrome, erythema multiforme, or toxic epidermal necrolysis.

Alpelisib may be associated with severe hyperglycemia, and healthcare professionals should check fasting glucose and hemoglobin A1c prior to treatment initiation. During treatment, patients should also be monitored for pneumonitis/interstitial lung disease and diarrhea.