This is for US residents only.

 

FoundationOne®CDx tissue-based and FoundationOne®Liquid CDx plasma-based are FDA-approved multi-gene tissue and plasma companion diagnostics for PIK3CA mutations.1,2

 

FoundationOne®CDx for tissue and FoundationOne®Liquid CDx for blood

 

FoundationOne®CDx for tissue1

An FDA-approved companion diagnostic that identifies PIK3CA mutations in advanced breast cancer patients who may be eligible for treatment with alpelisib for its FDA-approved indication. FoundationOne®CDx was approved as a companion diagnostic for alpelisib based on data from a clinical bridging study using specimens from patients screened for enrollment into SOLAR-1 study.

FoundationOne®CDx is a qualitative next-generation sequencing based in vitro diagnostic test for advanced cancer patients with solid tumors and is for prescription use only. The test analyzes 324 genes as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies in accordance with the approved 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 test 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 the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com.

 

 

 

 
 

 

FoundationOne®Liquid CDx for blood2

An FDA-approved companion diagnostic that identifies PIK3CA mutations in advanced breast cancer patients who may be eligible for treatment with alpelisib for its FDA-approved indication.

FoundationOne®Liquid CDx is for prescription use only and is a qualitative next-generation sequencing based in vitro diagnostic test for advanced cancer patients with solid tumors. The test analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes and as a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved 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 test does not guarantee a patient will be matched to a treatment.

A negative result does not rule out the presence of an alteration. Patients who 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 feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1CDxLabel.com.

 

FoundationOne®CDx tissue-based and FoundationOne®Liquid CDx blood-based are FDA-approved multi-gene tests for PIK3CA mutations

Test results samples

PIK3CA Mutation CDx findings using NGS are found on the first page of the report

Please see sample reports below.

Tissue-based CDx testing results

PIK3CA Positive FoundationOne®CDx sample report

PIK3CA Negative FoundationOne®CDx sample report

 

 

Blood-based CDx testing results

PIK3CA Positive FoundationOne®Liquid CDx sample report

PIK3CA Negative FoundationOne®Liquid CDx sample report

 

 

A negative result from a plasma specimen does not mean that the patient’s tumor is negative for genomic findings. Patients with a negative test result should be reflexed to routine biopsy, and their tumor mutation status confirmed using an FDA-approved tumor tissue test.

Preparing tissue samples:
FoundationOne®CDx tissue-based3

FFPE tumor tissue specimens are collected and prepared following standard pathology practices. FFPE specimens may be received either as unstained slides or as an FFPE block.

Acceptable samples3

  • FFPE specimens, including cut slide specimens, are acceptable

  • Use standard fixation methods to preserve nucleic acid integrity. Ten percent neutral-buffered formalin for 6 to 72 hours is industry standard. DO NOT use other fixatives (Bouins, B5, AZF, Holland’s)

  • Do not decalcify

 

Sample size

FoundationOne®CDx for tissue sample sizes

*For smaller samples, providing the original H&E will preserve material for testing.

 

Surface area

MINIMUM: 25 mm2

If sending slides, provide 10 unstained slides cut at 4-5 microns thick to achieve a tissue volume of 1 mm3†

Specimens with a smaller surface area may meet volume requirements by submitting additional unstained slides (USS) or block.

 

Tumor content

OPTIMUM: 30% tumor nuclei

MINIMUM: 20% tumor nuclei

Percent tumor nuclei (% TN) is the number of tumor cells divided by total number of all cells with nuclei.

Note for liver specimens: higher tumor content may be required because hepatocyte nuclei have twice the DNA content of other somatic nuclei.

The FFPE tissue block or 10 unstained slides + 1 H&E slide may be sent

 

Preparing blood samples:
FoundationOne®Liquid CDx blood-based4

Please use the blood collection tubes provided inside the FoundationOne®Liquid CDx Specimen Collection and Shipping Kit and do not cover the tube labels. Other tubes will not be accepted. You will be required to collect 2 tubes of peripheral whole blood (8.5mL per tube).

Levels of ctDNA may decrease after chemotherapy, and Foundation Medicine recommends that blood samples be drawn shortly before chemotherapy or at least 2 weeks after the previous treatment.

For complete collection instructions, please download Specimen Instructions from Foundation Medicine here.

 

NGS test overview

Limit of detection (LoD): tissue1

The LoD of alterations assessed by FoundationOne®CDx was evaluated. The LoD of PIK3CA E542K was determined and is summarized in the table below.

 

LoD for PIK3CA E542K1

 

Alteration
PIK3CA E542K
LoD§ allele fraction (%)
Based on the label (100% hit rate)
4.9%

 

§LoD calculation for PIK3CA E542K was based on the hit-rate approach, as there were fewer than three levels with hit rate between 10% and 90%. LoD from the hit-rate approach is defined as the lowest level with 100% hit rate (worst scenario).

 

LoD: blood-based2

 

LoD estimation for PIK3CA substitutions2

 

Alteration
PIK3CA substitutions
Number of samples evaluated
6
Median LoD
0.34% VAF

 

VAF, variant allele frequency.

 

Indication

PIQRAY® (alpelisib) 50mg, 150mg, 200mg 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 click here for full Prescribing Information.


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

References: 1. FoundationOne®CDx technical information. Foundation Medicine, Inc. 2. FoundationOne®Liquid CDx technical information. Foundation Medicine, Inc. 3. FoundationOne®CDx Specimen Instructions. https://assets.ctfassets.net/vhribv12lmne/6ms7OiT5PaQgGiMWue2MAM/53f9bdd91bfa22549087a28b53225fa5/F1_CDx_SpecimenInstructions_14.pdf. Accessed February 7, 2020. 4. FoundationOne®Liquid CDx Specimen Instructions. https://https://assets.ctfassets.net/w98cd481qyp0/2LUvDQvycj0iiF0BXCjZh5/9729216855dbc1ee4382b7495873233c/FoundationOne_Liquid_CDx_Specimen_Instructions.pdf. Accessed October 16, 2020.

 

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