PIK3CA Background

This is for US residents only.

PIK3CA mutations


PIK3CA is the most commonly mutated gene in HR+/HER2- advanced breast cancer1-4


40% of patients with HR_/HER2- advanced breast cancer have a PIK3CA mutation 40% of patients with HR_/HER2- advanced breast cancer have a PIK3CA mutation
Breast cancer patients with a PIK3CA mutation face a worse prognosis Breast cancer patients with a PIK3CA mutation face a worse prognosis


PIK3CA mutations can be detected in tissue or plasma specimens and are generally stable. Primary or metastatic breast cancer tumor tissue may be tested.7-9


The PI3K pathway

Hyperactive signaling in the PI3K pathway has been implicated in processes that contribute to the progression of breast cancer.10

PIK3CA pathway PIK3CA pathway

PIK3CA mutations may lead to hyperactivation of PI3Kα, a key upstream component of the PI3K pathway.10-12


How are PIK3CA mutations identified?

A companion diagnostic can be used to identify PIK3CA mutations. PIK3CA mutations are somatic mutations that occur along multiple domains. The companion diagnostic for identifying PIK3CA mutations detects 11 mutations in the PIK3CA gene which are listed in the table below.13


E545D [1635G>T only]


PIK3CA mutations can be detected using samples from primary breast tumor tissue, metastases, and plasma PIK3CA mutations can be detected using samples from primary breast tumor tissue, metastases, and plasma


PI3Kα, α-isoform of phosphatidylinositol-3-kinase.

Clinical relevance

Learn about the first and only therapy in combination with fulvestrant, specifically for postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen.1



PIQRAY® (alpelisib) tablets is indicated in combination with fulvestrant 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.

Important Safety Information
PIQRAY is contraindicated in patients with severe hypersensitivity to it or any of its components.

Severe Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and anaphylactic shock, were reported in patients treated with PIQRAY. Severe hypersensitivity reactions were manifested by symptoms including, but not limited to, dyspnea, flushing, rash, fever, or tachycardia. Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue PIQRAY in the event of severe hypersensitivity.

Severe Cutaneous Reactions: Severe cutaneous reactions, including Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) were reported. Do not initiate PIQRAY treatment in patients with a history of SJS, EM, or toxic epidermal necrolysis (TEN). Interrupt PIQRAY if signs or symptoms of severe cutaneous reactions are present (eg, a prodrome of fever, flu-like symptoms, mucosal lesions or progressive skin rash), until etiology of the reaction has been determined. Advise patients of the signs and symptoms of severe cutaneous reactions. Consider consultation with a dermatologist. Permanently discontinue PIQRAY if SJS, EM, or TEN is confirmed.

Hyperglycemia: Severe hyperglycemia, including ketoacidosis, was reported. Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment, monitor blood glucose and/or FPG at least once every week for the first 2 weeks, then at least once every 4 weeks, and as clinically indicated. Monitor HbA1c every 3 months and as clinically indicated. Initiate or optimize antihyperglycemic medications as clinically indicated. Interrupt, reduce dose, or discontinue PIQRAY if severe hyperglycemia occurs. The safety of PIQRAY in patients with type 1 and uncontrolled type 2 diabetes has not been established as these patients were excluded from the SOLAR-1 trial. Patients with a history of diabetes mellitus may require intensified diabetic treatment. Closely monitor patients with diabetes.

Advise patients of the signs and symptoms of hyperglycemia (eg, excessive thirst, urinating more often than usual or higher amount of urine than usual, or increased appetite with weight loss).

Pneumonitis: Severe pneumonitis, including acute interstitial pneumonitis and interstitial lung disease, has been reported in patients treated with PIQRAY. Monitor for clinical symptoms or radiological changes. Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams and in whom infectious, neoplastic, and other causes have been excluded by means of appropriate investigations. Interrupt or discontinue PIQRAY if severe pneumonitis occurs. Advise patients to immediately report new or worsening respiratory symptoms.  

Diarrhea: Severe cases of diarrhea, including dehydration and acute kidney injury, have been reported. Based on the severity of the diarrhea, PIQRAY may require dose interruption, reduction, or discontinuation. Advise patients to start antidiarrheal treatment, increase oral fluids, and notify their health care provider if diarrhea occurs while taking PIQRAY.

Embryo-Fetal Toxicity: PIQRAY and fulvestrant can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Also, refer to Full Prescribing Information of fulvestrant for pregnancy and contraception information.

Most common adverse reactions, including laboratory abnormalities (all grades, incidence ≥20%) were glucose increased (79%), creatinine increased (67%), diarrhea (58%), rash (52%), lymphocyte count decreased (52%), gamma glutamyl transferase increased (52%), nausea (45%), alanine aminotransferase increased (44%), fatigue (42%), hemoglobin decreased (42%), lipase increased (42%), decreased appetite (36%), stomatitis (30%), vomiting (27%), weight decreased (27%), calcium decreased (27%), glucose decreased (26%), activated partial thromboplastin time  prolonged (21%), and alopecia (20%).

Please click here for full Prescribing Information.

References: 1. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70. 2. 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. 3. Di Leo A, Johnston S, Seok Lee K, et al. Lancet Oncol. 2018;19(1):87-100. 4. Moynahan ME, Chen D, He W, et al. Br J Cancer. 2017;116(6):726-730. 5. 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. 6. Mosele F, Verret B, Jusque A, et al. Natural history and outcome of patients presenting a metastatic breast cancer with PIK3CA mutation. Abstract presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-Apr 3, 2019; Atlanta, GA. 7. Arthur LM, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat. 2014;147(1):211-219. 8. Piqray [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019. 9. Data on file. Novartis Pharmaceuticals Corp; 2018. 10. Al-Sukhun S, Lataifeh I, Al-Sukhun R. Defining the prognostic and predictive role of PIK3CA mutations: sifting through the conflicting data. Curr Breast Cancer Rep. 2016;8:73-79. 11. Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders and cancer. N Engl J Med. 2018;379(21):2052-2062. 12. Croessmann S, Sheehan JH, Lee KM, et al. PIK3CA C2 domain deletions hyperactivate phosphoinositide 3-kinase (PI3K), generate oncogene dependence, and are exquisitely sensitive to PI3Kα inhibitors. Clin Cancer Res. 2018;24(6):1426-1435. 13. therascreen® PIK3CA RGQ PCR Kit Instructions for Use. Germantown, MD: QIAGEN; May 2019.

9/19 PIQ-1214142