The US Food and Drug Administration (FDA) has approved alpelisib tablets (Piqray, Novartis), to be used together with the FDA-approved endocrine therapy fluvestrant, for the treatment of 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, according to an FDA news release.
A "companion" diagnostic test, therascreen PIK3CA RGQ PCR Kit (QIAGEN Manchester), was also approved for detection of the PIK3CA mutation in a tissue biopsy and/or a liquid biopsy. Patients who get a negative result on the therascreen test on a liquid biopsy should have PIK3CA mutation testing conducted on a tumor biopsy.
"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," Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in the news release.
The FDA's approval follows consideration of efficacy data from the SOLAR-1 trial, a randomized trial that included 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had advanced while or after being given an aromatase inhibitor.
The study found that the addition of alpelisib to fulvestrant significantly prolonged progression-free survival (median of 11 months vs 5.7 months) in those whose tumors had a PIK3CA mutation.
Frequently seen adverse effects are hyperglycemia, increased creatinine, diarrhea, rash, decreased serum lymphocyte count, elevated liver enzymes, nausea, vomiting, fatigue, low red blood cell count, increased lipase (enzymes released by the pancreas), decreased appetite, stomatitis, weight loss, low calcium levels, and prolonged activated partial thromboplastin time.
Clinicians should watch patients taking alpelisib for severe hypersensitivity reactions (intolerance), the FDA said in the news release. Patients taking alpelisib can develop potentially severe skin reactions such as rashes that may cause peeling and blistering of skin or mucous membranes including the lips and gums.
Healthcare professionals should not begin treatment for those with a history of Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, or other severe skin reactions.
Patients being treated with alpelisib have experienced severe hyperglycemia, and the safety of alpelisib in those with type 1 or uncontrolled type 2 diabetes is not known. The FDA advises healthcare professionals to obtain fasting glucose and HbA1c levels as well as optimize glycemic control.
Clinicians should monitor patients for pneumonitis/interstitial lung disease and diarrhea while undergoing treatment. The FDA requires that alpelisib be dispensed with a patient Medication Guide that explains important information about alpelisib's uses and risks.
"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 (RTOR) 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," Pazdur said.
The RTOR pilot program allows the FDA to start analyzing key efficacy and safety data sets before an application has been officially submitted, enabling the review team to start their review and communicate with the applicant earlier in the process.
The two pilot programs have put the approval of alpelisib approximately 3 months ahead of its August 18, 2019, Prescription Drug User Fee Act VI deadline.
This application was given Priority Review designation by the FDA.
Cite this: FDA OKs Alpelisib (Piqray), First PI3K Inhibitor for Breast Cancer - Medscape - May 24, 2019.