FDA approves Piqray, first PI3K inhibitor for advanced breast cancer

The FDA on Friday approved alpelisib, the first PI3K inhibitor to treat postmenopausal women and men with hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer that progressed during or after an endocrine-based regimen, according to an agency press release.

Alpelisib (Piqray, Novartis), used in combination with fulvestrant (Faslodex, AstraZeneca), was approved with a companion diagnostic test, therascreen PIK3CA RGQ PCR Kit (Qiagen), to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer,” 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 release. “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.”

Alpelisib, which was granted priority review designation, is the first new drug application for a new molecular entity approved under the Real-Time Oncology Review pilot program, Pazdur said, which permits the FDA to begin analyzing key efficacy and safety data sets before the official submission of an application, allowing the review team to begin its review and communicate with the applicant earlier. To speed approval, the agency also used the updated Assessment Aid pilot program, a multidisciplinary review template that helps focus the agency’s written review on “critical thinking and consistency” and reduces time spent on administrative tasks, Pazdur said.

“With these two pilot programs, today’s approval of Piqray comes approximately 3 months ahead of the Prescription Drug User Fee Act (PDUFA) VI deadline of August 18, 2019,” the agency stated in the release.

As HemOnc Today previously reported, patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer previously treated with endocrine therapy achieved longer PFS with alpelisib and fulvestrant compared with placebo and fulvestrant, according to results of a randomized, phase 3 trial published in The New England Journal of Medicine. Patients with PIK3CA mutations demonstrated median PFS of 11 months (95% CI, 7.5 -14.5) with alpelisib-fulvestrant vs. 5.7 months (95% CI, 3.7-7.4) with placebo-fulvestrant (HR for progression or death = 0.65; 95% CI, 0.5-0.85).

In the PIK3CA-mutated cohort, alpelisib-fulvestrant yielded a greater overall response rate (26.6%) vs. placebo-fulvesrant (12.8%), as well as a higher clinical benefit rate (61.5% vs. 45.3%) and a higher ORR among patients with measurable disease at baseline (35.7% vs. 16.2%).

“The FDA approval of Piqray, which was discovered at the Novartis Institutes for BioMedical Research, marks the first-ever treatment specifically for hormone receptor-positive/HER2-advanced breast cancer with a PIK3CA mutation,” Susanne Schaffert, PhD, CEO of Novartis Oncology, said in a company release. “We are proud to offer a new treatment option that specifically addresses the needs of the patients living with this mutation. We are grateful to our researchers’ bold and unrelenting pursuit of a first-in-class treatment for this incurable disease, and to the patients, investigators and administrators who participated in the clinical trials leading to this remarkable milestone.”

Common adverse effects of alpelisib are high blood glucose, an 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, decreased appetite, stomatitis, vomiting, weight loss, low calcium levels and hair loss.

Health care professionals are advised to monitor patients assigned alpelisib for severe hypersensitivity reactions. Patients are warned of potentially severe skin reactions, and health care professionals 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. Patients on alpelisib have reported severe hyperglycemia, and the safety of alpelisib in patients with type 1 or uncontrolled type 2 diabetes has not been established.

Before initiating treatment with alpelisib, 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 and diarrhea during treatment. Alpelisib must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks. – by Regina Schaffer

Disclosure s : Pazdur is 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. Schaffert is CEO of Novartis Oncology.

The FDA on Friday approved alpelisib, the first PI3K inhibitor to treat postmenopausal women and men with hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer that progressed during or after an endocrine-based regimen, according to an agency press release.

Alpelisib (Piqray, Novartis), used in combination with fulvestrant (Faslodex, AstraZeneca), was approved with a companion diagnostic test, therascreen PIK3CA RGQ PCR Kit (Qiagen), to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer,” 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 release. “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.”

Alpelisib, which was granted priority review designation, is the first new drug application for a new molecular entity approved under the Real-Time Oncology Review pilot program, Pazdur said, which permits the FDA to begin analyzing key efficacy and safety data sets before the official submission of an application, allowing the review team to begin its review and communicate with the applicant earlier. To speed approval, the agency also used the updated Assessment Aid pilot program, a multidisciplinary review template that helps focus the agency’s written review on “critical thinking and consistency” and reduces time spent on administrative tasks, Pazdur said.

“With these two pilot programs, today’s approval of Piqray comes approximately 3 months ahead of the Prescription Drug User Fee Act (PDUFA) VI deadline of August 18, 2019,” the agency stated in the release.

As HemOnc Today previously reported, patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer previously treated with endocrine therapy achieved longer PFS with alpelisib and fulvestrant compared with placebo and fulvestrant, according to results of a randomized, phase 3 trial published in The New England Journal of Medicine. Patients with PIK3CA mutations demonstrated median PFS of 11 months (95% CI, 7.5 -14.5) with alpelisib-fulvestrant vs. 5.7 months (95% CI, 3.7-7.4) with placebo-fulvestrant (HR for progression or death = 0.65; 95% CI, 0.5-0.85).

PAGE BREAK

In the PIK3CA-mutated cohort, alpelisib-fulvestrant yielded a greater overall response rate (26.6%) vs. placebo-fulvesrant (12.8%), as well as a higher clinical benefit rate (61.5% vs. 45.3%) and a higher ORR among patients with measurable disease at baseline (35.7% vs. 16.2%).

“The FDA approval of Piqray, which was discovered at the Novartis Institutes for BioMedical Research, marks the first-ever treatment specifically for hormone receptor-positive/HER2-advanced breast cancer with a PIK3CA mutation,” Susanne Schaffert, PhD, CEO of Novartis Oncology, said in a company release. “We are proud to offer a new treatment option that specifically addresses the needs of the patients living with this mutation. We are grateful to our researchers’ bold and unrelenting pursuit of a first-in-class treatment for this incurable disease, and to the patients, investigators and administrators who participated in the clinical trials leading to this remarkable milestone.”

Common adverse effects of alpelisib are high blood glucose, an 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, decreased appetite, stomatitis, vomiting, weight loss, low calcium levels and hair loss.

Health care professionals are advised to monitor patients assigned alpelisib for severe hypersensitivity reactions. Patients are warned of potentially severe skin reactions, and health care professionals 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. Patients on alpelisib have reported severe hyperglycemia, and the safety of alpelisib in patients with type 1 or uncontrolled type 2 diabetes has not been established.

Before initiating treatment with alpelisib, 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 and diarrhea during treatment. Alpelisib must be dispensed with a patient medication guide that describes important information about the drug’s uses and risks. – by Regina Schaffer

Disclosure s : Pazdur is 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. Schaffert is CEO of Novartis Oncology.