May 30, 2019 – The American Food and Drug Administration (FDA) recently approved Alpelisib (Piqray) to be used in combination with the FDA-approved 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 (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen.

Male breast cancer patient

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy (see here for companion tests approved by FDA). Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

According to Dr. Richard Pazdur of the FDA, Alpelisib (Piqray) is the first PIK3-inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments.

For this approval, FDA employed some of our newer regulatory tools to streamline reviews without compromising the quality of their assessment. Alpelisib (Piqray) is the first novel drug approved under the Real-Time Oncology Review (RTOR) pilot program. FDA also used an updated Assessment Aid (AAid), a multidisciplinary review template that helps focus the agencies  written review on critical thinking and consistency and reduces time spent on administrative tasks.

Metastatic breast cancer is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain). When breast cancer is hormone-receptor positive, patients may be treated with anti-hormonal treatment (also called endocrine therapy), alone or in combination with other medicines, or chemotherapy.

The efficacy of Alpelisib (Piqray) was studied in the SOLAR-1 clinical 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. Results from the trial showed the addition of Alpelisib (Piqray) to Fulvestrant (Faslodex) significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.

Male patient with TEN

Common side effects of Alpelisib (Piqray) are high blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), and hair loss.

As is true for many oncologic therapies, also Alpelisib (Piqray) comes with some very serious adverse effects. Thus, health care professionals are advised to monitor patients taking Alpelisib (Piqray) for severe hypersensitivity reactions (intolerance). Patients are warned of potentially severe skin reactions (rashes that may result in peeling and blistering of skin or mucous membranes like the lips and gums). Health care professionals are advised not to initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson Syndrome (SJS), erythema multiforme, or toxic epidermal necrolysis (TEN). Patients on Alpelisib (Piqray) have reported severe hyperglycemia (high blood sugar), and the safety of Alpelisib (Piqray) in patients with Type 1 or uncontrolled Type 2 diabetes has not been established. Before initiating treatment with Alpelisib (Piqray), health care professionals are advised to check fasting glucose and HbA1c, and to optimize glycemic control. Patients should be monitored for pneumonitis/interstitial lung disease (inflammation of lung tissue) and diarrhea during treatment. Alpelisib (Piqray) must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

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