Important Safety Information


PIQRAY® (alpelisib) tablets is contraindicated in patients with severe hypersensitivity to it or any of its components. Severe Hypersensitivity: Severe hypersensitivity reactions, including anaphy...

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Indication
PIQRAY 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.

PIK3CA Mutation Testing

Why to test?

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

Patients with a PIK3CA mutation face a worse prognosis.5,6

~40 of patients with HR+/HER2- aBC have a PIK3CA mutation
  • A meta-analysis of 1929 breast cancer cases with a range of breast cancer characteristics evaluated the impact PIK3CA mutations had on clinical outcomes, including progression-free survival, and found that the presence of a PIK3CA mutation was a negative prognostic factor (HR=1.67, 95% CI: 1.15-2.43; P=.007)5
  • PIK3CA mutations may be a mechanism of endocrine resistance7,8

 

Knowledge of PIK3CA mutation status can inform an up-front treatment plan for appropriate patients

When to test?

Test your HR+/HER2- aBC patients at initial MBC diagnosis9*

NCCN Clinical Practice Guidelines in Oncology (NCCN® Guidelines) include recommendations on when PIK3CA mutation testing should be considered
Assessment of PIK3CA mutation as part of initial MBC workup per NCCN Guidelines®

mBC, metastatic breast cancer.
*Following progression on or after an endocrine-based regimen.
†If liquid biopsy is negative, tumor tissue testing is recommended.
‡The safety of alpelisib in patients with type 1 or uncontrolled type 2 diabetes has not been established. 
§Category 1 is a designation indicating that, based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Adapted with permission from the NCCN Guidelines® for Breast Cancer V.4.2021. © 2021 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.

How to test?

PIK3CA mutations can be detected in tissue or plasma specimens10

  • PIK3CA mutations are generally stable; therefore, archival specimens and recent or new biopsies can be tested11,12
  • Primary or metastatic breast cancer tissue may be tested12

 

If PIK3CA mutation is not detected in a plasma specimen, retest the patient using tumor tissue

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.10,13-15

  • 11 different mutations in the PIK3CA gene as part of the FDA-approved indication for the PIK3CA companion diagnostic tests for PIQRAY
PIK3CA gene-functional domains

Negative results for PIK3CA mutation using plasma require further investigation

 

  • Up to 25% of tumors that have low-level DNA shedding may result in false negatives in plasma testing16-19
  • Up to 20% of plasma-based tests can lead to additional false negatives due to specimen handling20,21
  • 44% of patients (140/317) with PIK3CA mutations confirmed in tumor tissue and who had plasma specimen available for testing with the FDA-approved therascreen® PIK3CA RGQ PCR Kit did not have PIK3CA mutations identified in plasma10

For comprehensive background information, please visit the PIK3CA Testing Navigator.

Learn more

FDA-approved Companion Diagnostic (CDx) Tests

There are 3 FDA-approved PIK3CA mutation CDx tests available to eligible patients13-15:

  • QIAGEN's therascreen® PIK3CA RGQ PCR Kit is a real-time, qualitative, single-gene, polymerase chain reaction (PCR) test, run on the Rotor-Gene Q MDx (US) system, for the detection of 11 mutations in the PIK3CA gene and provides tissue and plasma testing
  • Foundation Medicine's FoundationOne®CDx and FoundationOne®Liquid CDx are comprehensive genomic profiling (CGP) next-generation sequencing (NGS) multi-gene tests, which include PIK3CA, and provide tissue and plasma testing, respectively

PIK3CA Mutation CDx Testing Program through NeoGenomics

NeoGenomics Laboratories will conduct tumor tissue and plasma testing using the QIAGEN therascreen® PIK3CA RGQ PCR Kit.13 Appropriate patients may receive one tumor tissue or plasma PIK3CA mutation test at no cost for the purpose of determining whether or not the patient has a PIK3CA mutation and is eligible for alpelisib for an FDA-approved indication, without regard to purchase of any prescribed drug or any other product.

If the patient tests negative for PIK3CA mutation using plasma, eligible patients may also receive one PIK3CA reflex tissue test at no cost. No patient, health care program, or beneficiary shall be billed for this mutation test. The test shall not be included in a bundled payment to any health care facility including, but not limited to, a hospital. The ordering physician shall not be compensated any fees in connection with this mutation testing, such as for specimen collection, handling, or data reporting. Program is not valid where prohibited by law. Novartis reserves the right to rescind, revoke, or amend the program without notice.

If no mutation is detected in a plasma specimen, retest the patient with tumor tissue.

The QIAGEN therascreen® PIK3CA RGQ PCR Kit has been verified for both tumor tissue and plasma testing with NeoGenomics Laboratories.

Health care professional testing results

Neogenomics PIK3CA mutation CDx testing program HCP sample report

Patient-friendly testing results

Neogenomics PIK3CA mutation CDx testing program  patient sample report

Online Ordering at NeoLINK®|| is the preferred ordering method when using NeoGenomics Laboratories.

Order tests online through NeoLINK®
Neogenomics ordering process

Schedule your specimen pickup by calling Client Services at 1-866-776-5907, option #1.

More details about this program can be found in the PIK3CA Mutation CDx Testing Program brochure.

Go to brochure

NeoGenomics is the only lab currently performing testing under the PIK3CA Mutation CDx Testing Program. Alternate labs will process this test outside of the PIK3CA Mutation CDx Testing Program.

Find alternate lab

Multi-gene NGS test from Foundation Medicine

FoundationOne®CDx and FoundationOne®Liquid CDx multi-gene tissue and plasma testing programs

FoundationOne®CDx tissue-based14
FoundationOne®CDx is a comprehensive genomic profiling (CGP) next-generation sequencing (NGS)-based multi-gene in vitro diagnostic test. FoundationOne®CDx can detect PIK3CA mutations in tissue and is a companion diagnostic for alpelisib.

See FoundationOne®CDx Technical and Safety Information

Results can be found on page 1 of the sample report.

FoundationOne®CDx sample report

FoundationOne®Liquid CDx blood-based15
FoundationOne®Liquid CDx is a comprehensive genomic profiling (CGP) next-generation sequencing (NGS)-based multi-gene in vitro diagnostic test. FoundationOne®Liquid CDx can detect PIK3CA mutations in blood and is a companion diagnostic for alpelisib. Foundation Medicine offers the option to automatically reflex between tissue and liquid sample types.

See FoundationOne®Liquid CDx Technical and Safety Information

Results can be found on page 1 of the sample report.

FoundationOne®Liquid CDx sample report
FoundationOne®CDx and FoundationOne®Liquid CDx are covered by Original Medicare and Medicare Advantage for qualifying beneficiaries
  • Foundation Medicine offers in-home blood draw with mobile phlebotomy through its partner, ExamOne®, to support broader access to FoundationOne®Liquid CDx, at no additional cost

Novartis is not responsible for any such third party content that may be accessed via the above provided resources. Novartis does not endorse the content contained in these sites, nor the organizations publishing those sites, and hereby disclaims any responsibility for such content.

Foundation Medicine generally expects to provide results in 10 days or less from specimen receipt.
See more at Foundation Medicine

Single-gene testing (PCR) with QIAGEN therascreen® PIK3CA RGQ PCR Kit

QIAGEN therascreen® PIK3CA RGQ PCR Kit

The QIAGEN therascreen® PIK3CA RGQ PCR Kit is an FDA-approved companion diagnostic (CDx) single-gene test for the detection of 11 mutations in the PIK3CA gene using genomic DNA (gDNA) extracted from formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue or circulating tumor DNA (ctDNA) isolated from K2EDTA anticoagulated peripheral whole blood plasma taken from patients with breast cancer.1

For information on using the QIAGEN therascreen® PIK3CA RGQ PCR Kit, please see Instructions for Use (IFU).

QIAGEN therascreen® PIK3CA RGQ PCR Kit IFU
The QIAGEN therascreen® PIK3CA RGQ PCR Kit has been verified for both tumor tissue and plasma testing with NeoGenomics Laboratories

NeoGenomics is the only lab currently performing testing under the PIK3CA Mutation CDx Testing Program. Alternate labs will process this test outside of the PIK3CA Mutation CDx Testing Program.

To find alternate labs that have verified the QIAGEN therascreen® PIK3CA RGQ PCR Kit, visit the QIAGEN lab finder online or call 1-800-362-7737
Find alternate lab

Testing Resources

Download the PIK3CA Testing Navigator Brochure
Download the PIK3CA CDx Testing Program Brochure

||This is an external website independently operated and not managed by Novarits Pharmaceuticals Corporation. Novartis assumes no responsibility for the site.

 

PIK3CA Testing Navigator Site

For more detailed testing information, please visit our comprehensive PIK3CA Testing Navigator.
Start here

FoundationOne®CDx and FoundationOne®Liquid CDx are qualitative next-generation sequencing based in vitro diagnostic tests for advanced cancer patients with solid tumors and are for prescription use only. FoundationOne CDx utilizes FFPE tissue and analyzes 324 genes as well as genomic signatures. FoundationOne Liquid CDx analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes. The tests are companion diagnostics to identify patients who may benefit from treatment with specific therapies in accordance with the therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the tests does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy for testing with FoundationOne CDx when archival tissue is not available which may pose a risk. Patients who are tested with FoundationOne Liquid CDx and are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if available. For the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com and www.F1LCDxLabel.com.

therascreen is a registered trademark of QIAGEN group.

Foundation Medicine, FoundationOne CDx, and FoundationOne Liquid CDx are registered trademarks of Foundation Medicine, Inc.

ExamOne is a registered trademark of Quest Diagnostics.

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, Stefanovska B, Lusque A, et al. Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol. 2020;31(3):377-386. 7. Liu J, Jing L, Wang Y, et al. Clinical and genetic risk factors for fulvestrant treatment in post-menopause ER-positive advanced breast cancer patients. J Transl Med. 2019;17(27):1-13. 8. Mayer IA, Abramson VG, Formisano L, et al. A phase Ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2- metastatic breast cancer. Clin Cancer Res. 2017;23(1):26-34.  https://doi.org/10.1016/j.annonc.2019.11.006. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2021. © 2021 National Comprehensive Cancer Network, Inc. All rights reserved. Accessed April 30, 2021. To view the most recent and complete version of the guideline, go online to: NCCN.org. 10. Piqray [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020. 11. 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. 12. Data on file. Novartis Pharmaceuticals Corp; 2018. 13. therascreen® PIK3CA RGQ PCR Kit Instructions for Use. Germantown, MD: QIAGEN; May 2019. 14. FoundationOne®CDx technical information. Foundation Medicine, Inc. 15. FoundationOne®Liquid CDx technical information. Foundation Medicine, Inc. 16. Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014; 6(224):224ra24. 17. Diaz LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Onc. 2014;32(6):579-586. 18. Abbosh C, Birkbak NJ, Swanton C. Early stage NSCLC–challenges to implementing the ctDNA-based screening and MRD detection. Nat Rev Clin Oncol. 2018;15(9):577-586. 19. Sacher AG, Komatsubara KM, Oxnard GR. Application of plasma genotyping technologies in non-small cell lung cancer: a practical review. J Thorac Onc. 2017;12(9):1344-1356. 20. Lippi G, Chance JJ, Church S, et al. Preanalytical quality improvement: from dream to reality. Clin Chem Lab Med. 2011;49(7):1113-1126. 21. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists joint review. J Clin Oncol. 2018;36(16):1631-1641. 22. Billing and Financial Assistance. Accessed February 12, 2021. https://www.foundationmedicine.com/resource/billing-and-financial-assistance.

 

 

Indication

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, can occur in patients treated with PIQRAY. Severe hypersensitivity reactions were manifested by symptoms including, but not limited to, dyspnea, flushing, rash, fever, or tachycardia. The incidence of grade 3 and 4 hypersensitivity reactions was 0.7%. Advise patients of the signs and symptoms of severe hypersensitivity reactions. Permanently discontinue PIQRAY in the event of severe hypersensitivity.

Severe Cutaneous Adverse Reactions (SCARs): SCARs including Stevens-Johnson syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) can occur in patients treated with PIQRAY. In the SOLAR-1 study, SJS and EM were reported in 0.4% and 1.1% of patients, respectively. DRESS was reported in patients in the postmarketing setting. If signs or symptoms of SCARs occur, interrupt PIQRAY until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended.

If a SCAR is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous SCARs during PIQRAY treatment. If it is not confirmed, PIQRAY may require dose modifications, topical corticosteroids, or oral antihistamine treatment.

Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy).

Hyperglycemia: Severe hyperglycemia, including ketoacidosis, can occur in patients treated with PIQRAY. Hyperglycemia was reported in 65% of patients treated with PIQRAY. Grade 3 (FPG >250-500 mg/dL) and grade 4 (FPG >500 mg/dL) hyperglycemia were reported in 33% and 3.9% of patients, respectively. Ketoacidosis was reported in 0.7% of patients (n=2) treated with PIQRAY.

Before initiating treatment with PIQRAY, test fasting plasma glucose (FPG), HbA1c, and optimize blood glucose. After initiating treatment with PIQRAY, monitor fasting glucose (FPG or fasting blood glucose) 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. If a patient experiences hyperglycemia after initiating treatment with PIQRAY, monitor fasting glucose as clinically indicated, and at least twice weekly until fasting glucose decreases to normal levels. During treatment with antidiabetic medication, continue monitoring fasting glucose at least once a week for 8 weeks, followed by once every 2 weeks and as clinically indicated. Consider consultation with a health care practitioner with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes.

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 medical history of type 2 diabetes were included. Patients with a history of diabetes mellitus may require intensified diabetic treatment. Closely monitor patients with diabetes.

Based on the severity of the hyperglycemia, PIQRAY may require dose interruption, reduction, or discontinuation. 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, can occur in patients treated with PIQRAY. Pneumonitis was reported in 1.8% of patients treated with PIQRAY.

In patients who have new or worsening respiratory symptoms or are suspected to have developed pneumonitis, interrupt PIQRAY immediately and evaluate the patient for pneumonitis. Consider a diagnosis of noninfectious pneumonitis in patients presenting with nonspecific 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.

Permanently discontinue PIQRAY in all patients with confirmed pneumonitis. Advise patients to immediately report new or worsening respiratory symptoms.

Diarrhea: Severe diarrhea, including dehydration and acute kidney injury, can occur in patients treated with PIQRAY. Most patients (58%) experienced diarrhea during treatment with PIQRAY. Grade 3 diarrhea occurred in 7% (n=19) of patients. 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: Based on findings in animals and its mechanism of action, PIQRAY can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with PIQRAY and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use condoms and effective contraception during treatment with PIQRAY and for 1 week after the last dose. Refer to the full Prescribing Information of fulvestrant for pregnancy and contraception information.

The most common adverse reactions (all grades, incidence ≥20%) were diarrhea (58%), rash (52%), nausea (45%), fatigue (42%), decreased appetite (36%), stomatitis (30%), vomiting (27%), weight decreased (27%), and alopecia (20%). The most common grade 3/4 adverse reactions (incidence ≥2%) were rash (20%), diarrhea (7%), fatigue (5%), weight decreased (3.9%), nausea (2.5%), stomatitis (2.5%), and mucosal inflammation (2.1%).

The most common laboratory abnormalities (all grades, incidence ≥20%) were glucose increased (79%), creatinine increased (67%), lymphocyte count decreased (52%), gamma-glutamyl transferase (GGT) increased (52%), alanine aminotransferase (ALT) increased (44%), hemoglobin decreased (42%), lipase increased (42%), calcium decreased (27%), glucose decreased (26%), and activated partial thromboplastin time (aPTT) prolonged (21%). The most common grade 3/4 laboratory abnormalities (incidence ≥5%) were glucose increased (39%), GGT increased (11%), lymphocyte count decreased (8%), lipase increased (7%), and potassium decreased (6%).

Please see full Prescribing Information.