?Piqray (alpelisib) is the only treatment approved specifically to address PIK3CA mutation, underscoring Novartis commitment to reimagining cancer care
?Approval based on SOLAR-1 Phase III trial showing Piqray plus fulvestrant nearly doubled median PFS (11.0 vs. 5.7 months), compared to fulvestrant alone1,2
?334,000 people are diagnosed with advanced breast cancer worldwide each year, and approximately 40% of those with HR+/HER2- subtype have a PIK3CA mutation, which is associated with a poor prognosis3-12

Basel, July 29, 2020 — Novartis today announced the European Commission (EC) has approved Piqray® (alpelisib) 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-) locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy. Piqray is the first and only treatment specifically approved for people with advanced breast cancer whose tumors harbor a PIK3CA mutation, which stimulates tumor growth and is associated with poor response to therapy13.

“Piqray is an important new therapy for HR+/HER2- advanced breast cancer patients whose tumors have a PIK3CA mutation, and we look forward to making it available in countries across Europe,” said Kees Roks, Head Region Europe, Novartis Oncology. “Knowledge of PIK3CA status can better equip doctors as they develop a personalized upfront treatment plan for patients. Piqray offers new hope for advanced breast cancer patients with a PIK3CA mutation, who typically face a worse overall prognosis.”

This approval follows a positive opinion granted in May by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based on the Phase III SOLAR-1 trial showing that Piqray nearly doubled median progression-free survival (PFS) compared to fulvestrant alone1,2. Overall response rate, 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 compared to fulvestrant alone1,2. Read more about the positive CHMP opinion and the SOLAR-1 clinical trial results here.

Patients with HR+/HER2- advanced breast cancer should be selected for treatment with Piqray based on the presence of a PIK3CA mutation in tumor or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, tumor tissue should be tested if available.

About Piqray® (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen. Piqray is approved in 48 countries, including the US and European member states.

Important Safety Information from the PIQRAY EU SmPC
The most common ADRs and the most common grade 3 / 4 ADRs (reported at a frequency >20% and ?2%, respectively) were plasma glucose increased, creatinine increased, gamma-glutamyltransferase increased, rash, lymphocyte count decreased, nausea, alanine aminotransferase increased, anaemia, fatigue, lipase increased, decreased appetite*, stomatitis, vomiting*, weight decreased, hypocalcaemia, plasma glucose decreased*, activated partial thromboplastin time prolonged*, alopecia**, diarrhoea, hypokalaemia, hypertension, nausea, creatinine increased, and mucosal inflammation (*<2% grade 3/4 ADRs reported, ** no grade 3/4 ADRs reported).

Piqray can cause serious side effects such as severe hypersensitivity, severe cutaneous reactions, hyperglycaemia, pneumonitis, diarrhoea, and osteonecrosis of the jaw.

The following should be taken into consideration prior to or during treatment with Piqray:

Piqray should be permanently discontinued in patients with serious hypersensitivity reactions.

Piqray should not be initiated in patients with a history of severe cutaneous reactions, should be interrupted if signs or symptoms of severe cutaneous reactions are present, and permanently discontinued if a severe cutaneous reaction is confirmed.

Fasting glucose and HbA1c levels should be monitored frequently in the first 4 weeks of treatment, and patients should be advised of the signs and symptoms of hyperglycaemia.

In case of new or worsening respiratory symptoms, the patient should be evaluated for pneumonitis.

Patients should be advised to notify their physician if diarrhoea occurs.

Caution should be exercised when Piqray and bisphosphonates or denosumab are used together or sequentially. Piqray should not be initiated in patients with ongoing osteonecrosis of the jaw.

The efficacy and safety of Piqray has not been studied in patients with symptomatic visceral disease.

Animal studies suggest that Piqray may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Piqray during treatment and at least 1 week after stopping treatment. Women should not breast feed for at least 1 week after the last dose of Piqray. Piqray may affect fertility in males and females.

Please download full Summary of Product Characteristics for Piqray here?.

Disclaimer
This media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” etc. etc..
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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. Globocan 2018 (WHO), Cancer Today: Estimated number of new cases in 2018, worldwide, females, all ages_1_ 2018.
4. Gheorghe D. Breast Cancer. Decision Resources. July 2017:1-338.
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.
13. Thomssen, C., et al. (2020, February 10). International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus – Assessment by a German Group of Experts. Retrieved June 16, 2020, from https://www.karger.com/Article/FullText/505957?

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