On May 24, 2019, the FDA approved Piqray (alpelisib; Novartis), an oral PIK3 inhibitor, in combination with endocrine therapy with fulvestrant (Faslodex), for the treatment of postmenopausal women, as well as men, with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer and PIK3CA mutation (as detected by an FDA-approved test) that progressed during or after an endocrine-based treatment regimen. The FDA used its priority review designation to consider the application of alpelisib.
At the same time, the FDA approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients whose liquid biopsy result with therascreen is negative should have a tissue-based biopsy for PIK3CA mutation.
“Piqray is the first PI3K 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,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real-Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks,” Dr Pazdur added.
The efficacy of alpelisib was evaluated in SOLAR-1, a randomized clinical trial of 572 postmenopausal women as well as men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed during or after an aromatase inhibitor therapy. The combination of alpelisib plus fulvestrant significantly prolonged progression-free survival (PFS) compared with fulvestrant alone, for a median PFS of 11 months versus 5.7 months, respectively, in patients whose tumors had a PIK3CA mutation.
The adverse reactions, including some severe reactions, reported with alpelisib are hyperglycemia (which could be severe), increased creatinine level, diarrhea, rash, decreased lymphocyte count, elevated liver enzymes, nausea, fatigue, low red blood cell count, increased lipase level, decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, acquired thrombotic thrombocytopenic purpura, and hair loss. The drug must not be dispensed without a Medication Guide that describes the medication’s potential risks.
Alpelisib is the first new molecular entity for which a New Drug Application was submitted and approved by the FDA under the Real-Time Oncology Review pilot program, which allows the FDA to expedite the approval process by analyzing a drug’s key efficacy and safety data before the official submission of a drug application. The FDA also used its updated Assessment Aid, which helps to focus the FDA’s written review on critical thinking. Using these processes allowed the FDA to approve alpelisib approximately 3 months ahead of its PDUFA deadline.
