- Piqray (alpelisib, formerly BYL719) plus fulvestrant nearly doubled median PFS (11.0 vs 5.7 months) in HR+/HER2- advanced breast cancer patients with a PIK3CA mutation compared to fulvestrant alone in the SOLAR-1 clinical trial[1],[2],[3],[4]
- ~40% of HR+/HER2- advanced breast cancer patients may face worse disease prognosis due to presence of PIK3CA mutations in their tumors[5],[6],[7],[8],[9]
- Piqray was the first new drug application approved under the FDA Oncology Center of Excellence Real-Time Oncology Review pilot program
BASEL, Switzerland I May 24, 2019 I Novartis today announced the US Food and Drug Administration (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 (HR+/HER2-), PIK3CA-mutated, advanced or metastatic breast cancer, as detected by an FDA-approved test following progression on or after an endocrine-based regimen[1].
PIK3CA is the most commonly mutated gene in HR+/HER2- breast cancer; approximately 40% of patients living with HR+/HER2- breast cancer have this mutation[8],[10]. PIK3CA mutations are associated with tumor growth, resistance to endocrine treatment and a poor overall prognosis[11],[12]. Piqray targets the effect of PIK3CA mutations and may help overcome endocrine resistance in HR+ advanced breast cancer.
“The FDA approval of Piqray, which was discovered at the Novartis Institutes for BioMedical Research, marks the first ever treatment specifically for HR+/HER2- advanced breast cancer with a PIK3CA mutation. We are proud to offer a new treatment option that specifically addresses the needs of the patients living with this mutation,” said Susanne Schaffert, PhD, CEO, Novartis Oncology. “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.”
FDA approval is based on results of the Phase III trial, SOLAR-1, that showed Piqray plus fulvestrant nearly doubled median progression-free survival (PFS) 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)[2]. Piqray provided consistent PFS results across pre-specified subgroups, including among patients previously treated with a CDK4/6 inhibitor[2],[3].
Overall response rate (ORR), an indicator of the proportion of patients who experience at least a 30% reduction in overall tumor size (in patients with measurable disease), was 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)[2]. 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, MD, PhD, research director and head of INSERM Unit U981, professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France, and global SOLAR-1 principal investigator. “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.
“If you are facing a complex disease like metastatic breast cancer, you want to follow a path that is specific to your type of disease,” said Shirley Mertz, President, Metastatic Breast Cancer Network. “Finding the right treatment team and getting the right tests, like testing for the PIK3CA mutation, will help your healthcare team identify accurate, precise treatment options for your disease.”
Novartis is committed to providing patients with access to medicines, as well as resources and support to address a range of needs. The Novartis Oncology Patient Support Program is available to help guide eligible patients through the various aspects of getting started on treatment, from providing educational information to helping them understand their insurance coverage and identify potential financial assistance options. For more information, patients and healthcare professionals can call 1-800-282-7630.
Full prescribing information for Piqray can be found at https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/piqray.pdf.
About Piqray® (alpelisib)
Piqray is a kinase inhibitor approved in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer, as detected by an FDA-approved test following progression on or after endocrine-based regimen[1].
Approximately 40% of HR+ advanced breast cancer patients have a mutation that may activate the PI3K-alpha isoform, called PIK3CA mutations[5],[6],[7],[8]. These mutations are associated with resistance to endocrine therapy, disease progression and a poor prognosis[11],[12]. Piqray works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform, to address the effect of PIK3CA mutations.
About SOLAR-1
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[1],[2],[3]. 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[1],[2],[3]. 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, and additional 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[1],[2],[3]. SOLAR-1 is ongoing to assess overall survival and other secondary endpoints.
About Novartis in Advanced Breast Cancer
For more than 30 years, Novartis has been tackling breast cancer with superior science, great collaboration and a passion for transforming patient care. With one of the most diverse breast cancer pipelines and one of the largest numbers of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.
Indication
PIQRAY® (alpelisib) tablets is a prescription medicine used in combination with the medicine fulvestrant to treat women who have gone through menopause and men who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer or breast cancer that has spread to other parts of the body (metastatic), with an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) gene, and whose disease has progressed on or after endocrine therapy. Your health care provider will test your cancer for an abnormal “PIK3CA” gene to make sure that PIQRAY is right for you. It is not known if PIQRAY is safe and effective in children.
About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 105 000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com.
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References
[1] Piqray (alpelisib) Prescribing Information. East Hanover., New Jersey, USA: Novartis Pharmaceuticals Corporation; May 2019.
[2] André F, Ciruelos E, Rubovszky G. Alpelisib for PIK3CA-Mutated, Hormone-Receptor-Positive Advanced Breast Cancer. N Eng J Med 2019.
[3] André F, Ciruelos EM, Rubovszky G et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): Results of the phase III SOLAR-1 trial. Annals of Oncology, Vol 29, Suppl 8, October 2018, Abstract LBA3_PR.
[4] Juric D, Ciruelos EM, Rubovszky G et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): Phase 3 SOLAR-1 trial results. Presented at the San Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08) on December 6, 2018.
[5] Tolaney S, Toi M, Neven P, et al. Presented at: 2019 American Association for Cancer Research (AACR) Annual Meeting; March 29-April 3, 2019; Atlanta, GA.
[6] Di Leo A, Johnston S, Seok Lee K, et al. Lancet Oncol. 2018;19(1):87-100.
[7] Moynahan ME, Chen D, He W, et al. Br J Cancer. 2017;116(6):726-730002E
[8] The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70.
[9] Sobhani N, Roviello G, Corona SP et al. The prognostic value of PI3K mutational status in breast cancer: a meta-analysis. J Cell Biochem. 2018;119(6):4287-4292.
[10] Sabine V, Crozier C, Brookes C, et al. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. Journal of Clinical Oncology. 2014;32:2951-2958.
[11] Miller TW, Rexer BN, Garrett JT, et al. Mutations in the Phosphatidylinositol 3-Kinase Pathway: Role in Tumor Progression and Therapeutic Implications in Breast Cancer. Breast Cancer Res. 2011.
[12] Saal LH, Johansson P, Holm K. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. PNAS. 2007;104(18):7564-7569.
SOURCE: Novartis
