FDA has approved Piqray (alpelisib, formerly BYL719) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor positive, human epidermal growth factor receptor-2 negative, PIK3CA-mutated, advanced or metastatic breast cancer, as detected by an FDA-approved test following progression on or after an endocrine-based regimen.
Piqray is sponsored by Novartis.
Approximately 40% of patients living with HR+/HER2- breast cancer have PIK3CA. PIK3CA mutations are associated with tumor growth, resistance to endocrine treatment, and a poor overall prognosis. Piqray targets the effect of PIK3CA mutations and may help overcome endocrine resistance in HR+ advanced breast cancer.
FDA approval is based on the results of the phase III trial, SOLAR-1, that showed Piqray plus fulvestrant nearly doubled median progression-free survival compared to fulvestrant alone in HR+/HER2- advanced breast cancer patients with a PIK3CA mutation (median PFS 11.0 months vs. 5.7 months; HR=0.65, 95% CI: 0.50-0.85; p<0.001). Piqray provided consistent PFS results across pre-specified subgroups, including among patients previously treated with a CDK4/6 inhibitor.
Overall response rate more than doubled when Piqray was added to fulvestrant in patients with a PIK3CA mutation (ORR= 35.7% vs 16.2% for fulvestrant alone, p=0.0002).
Piqray and its associated companion diagnostic test from QIAGEN N.V. was the first combination product approved under the FDA Oncology Center of Excellence Real-Time Oncology Review pilot program.
“Today’s approval is expected to change the way we practice medicine in advanced breast cancer. For the first time, physicians can test for PIK3CA biomarkers and develop a treatment plan based on the genomic profile of a patient’s cancer,” said Fabrice André, global SOLAR-1 principal investigator, research director and head of INSERM Unit U981, professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France.
“In the SOLAR-1 phase III trial, alpelisib plus fulvestrant nearly doubled median PFS and more than doubled overall response rate in patients with a PIK3CA mutation, offering them new hope for longer life without progression.”
Patients with HR+/HER2- advanced breast cancer can be selected for treatment with Piqray based on the presence of PIK3CA mutations. Concurrent with the approval of Piqray, the therascreen PIK3CA companion diagnostic test from QIAGEN was also approved by the FDA and is now available for patient testing.
SOLAR-1 is a global, phase III randomized, double-blind, placebo-controlled trial studying Piqray in combination with fulvestrant for postmenopausal women, and men, with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor. SOLAR-1 is the pivotal phase III trial that supported this approval.
The trial randomized 572 patients. Patients were allocated based on central tumor tissue assessment to either a PIK3CA-mutated cohort (n=341) or a PIK3CA non-mutated cohort (n=231).
Within each cohort, patients were randomized in a 1:1 ratio to receive continuous oral treatment with Piqray (300 mg once daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or placebo plus fulvestrant.
Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment. Patients and investigators are blinded to PIK3CA mutation status and treatment.
The primary endpoint is local investigator assessed PFS using RECIST 1.1 for patients with a PIK3CA mutation. The key secondary endpoint is overall survival. Secondary endpoints include, but are not limited to, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutated cohort, safety, and tolerability. SOLAR-1 is ongoing to assess overall survival and other secondary endpoints.
