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.

Safety Profile

Serious and Common Adverse Reactions (ARs)

  • Serious ARs associated with PIQRAY® (alpelisib) tablets include severe hypersensitivity, severe cutaneous adverse reactions (SCARs), hyperglycemia, pneumonitis, diarrhea, and embryo-fetal toxicity1
ARs occurring in >20% of the total population
ARs
PIQRAY + fulvestrant (n=284)
All grades (%)
Grade 3-4 (%)
Placebo + fulvestrant (n=287)
All grades (%)
Grade 3-4 (%)
Gastrointestinal disorders
Diarrhea

58

7*

16

0.3*

Nausea

45

2.5*

22

0.3*

Stomatitisa

30

2.5*

6

0*

Vomiting

27

0.7*

10

0.3*

General disorders and administration site conditions
Fatigueb

42

5*

29

1*

Investigations
Weight decreased

27

3.9*

2.1

0*

Metabolism and nutrition disorders
Decreased appetite

36

0.7*

10

0.3*

Skin and subcutaneous tissue disorders
Rashc

52

20*

7

0.3*

 

*No grade 4 ARs were reported.
aIncluding stomatitis, aphthous ulcer, mouth ulceration.
bIncluding fatigue, asthenia.
cIncluding rash, rash maculo-papular, rash macular, rash generalized, rash papular, rash pruritic.

Laboratory abnormalities occurring in >30% of the total population
Laboratory abnormality
PIQRAY + fulvestrant (n=284)
All grades (%)
Grade 3-4 (%)
Placebo + fulvestrant (n=287)
All grades (%)
Grade 3-4 (%)
Hematological parameters
Lymphocyte count decreased

52

8

40

4.5

Hemoglobin decreased

42

4.2

29

1

Biochemical parameters
Glucose increaseda

79

39

34

1

Creatinine increased

67

2.8

25

0.7

Gamma Glutamyl Transferase (GGT) increased

52

11

44

10

Alanine Aminotransferase (ALT) increased

44

3.5

34

2.4

Lipase increased

42

7

25

6

 

No grade 4 laboratory abnormalities were reported.
aGlucose increase is an expected laboratory abnormality of PI3K inhibition.

 

  • Glucose increase, which may include hyperglycemia, is an expected, on-target effect of PI3K inhibition1-3
  • Hyperglycemia, a laboratory-related AR, was reported in 65% of patients treated with PIQRAY (grade 3=33%; grade 4=3.9%)1
  • Among patients treated with PIQRAY and fulvestrant, 5% permanently discontinued both therapies and 21% permanently discontinued PIQRAY alone due to ARs1
    • The most common ARs leading to discontinuation of PIQRAY were hyperglycemia (6% of patients), rash (4%), diarrhea (3%), and fatigue (3%)1
  • Dose reductions due to ARs occurred in 55% of patients receiving PIQRAY and fulvestrant1
    • The most common ARs leading to a dose reduction of PIQRAY were hyperglycemia (29% of patients), rash (9%), diarrhea (6%), stomatitis (4%), and mucosal inflammation (2%)1

 

KEEPING TRAQ With PIQRAY

KEEPING TRAQ With PIQRAY

Everything you need to know about the safety profile and managing and monitoring selected adverse reactions (ARs) is a few clicks away.

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Managing Patients on PIQRAY Video

LEARN ABOUT PATIENT MANAGEMENT

Dr Dejan Juric, Director of the Termeer Center for Targeted Therapies and Program Director of the Investigational Cancer Therapeutics Program at the Massachusetts General Hospital, discusses important management information for patients on PIQRAY. Watch the video to learn more.

Managing your patient on PIQRAY brochure

Download the brochure to learn how to manage selected ARs associated with PIQRAY, should they occur.

Download Brochure

Hyperglycemia and cutaneous adverse reaction monitoring and consideration checklist

Download the checklist to learn about monitoring patients before and during treatment with PIQRAY.

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Cutaneous Adverse Reaction Monitoring and Considerations

 
Consider prophylaxis with antihistamines prior to onset of rash
  • Antihistamines administered prior to rash onset may decrease incidence and severity of rash based on SOLAR-1 trial1

Effects of prophylactic treatment, including antihistamines, prior to onset of rash in patients receiving PIQRAY + fulvestrant1

Event
Patients receiving prophylactic treatment prior to onset of rash (n=86)
Overall population (n=284)
All grades rash
27%
54%
Grade 3 rash
12%
20%
Rash leading to permanent discontinuation of PIQRAY
3.5%
4.2%

 

Advise patients of signs and symptoms of severe cutaneous adverse reactions (SCARs) and to immediately contact their health care provider should they occur1
  • Signs and symptoms include a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy1
Monitor for different forms of rash
  • Rash may present in different forms including rash, rash maculopapular, rash macular, rash generalized, rash papular, and rash pruritic1
  • Maculopapular rash was reported as one of the most common types of rash2

In the SOLAR-1 study

Median time to first occurrence of grade 2 or 3 rash was 12 days

Median time to first onset of grade 2 or 3 rash1

If a SCAR is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous SCAR during treatment

Refer to PIQRAY prescribing Information and/or the Patient Management Brochure for management recommendations and medication used for rash in the SOLAR-1 trial

Hyperglycemia Monitoring and Considerations

Assess FPG and HbA1c1

FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin.

Optimize blood glucose1
  • In the SOLAR-1 trial, patients with controlled type 2 diabetes and prediabetes were included if they had an FPG of <140 mg/dL (7.7 mmol/L) and HbA1c of ≤6.4% (both criteria had to be met)2
Assess patient's past medical history
  • 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 included1
  • Patients with a history of diabetes mellitus may require intensified diabetic treatment. Closely monitor patients with diabetes1
Advise patients of the following signs and symptoms of hyperglycemia and to contact their health care provider immediately should they occur1
  • Excessive thirst, urinating more often than usual or higher amount of urine than usual, or increased appetite with weight loss1
Test fasting glucose as recommended.
(FPG or fasting blood glucose)

First 2 weeks:
At least 1x per week1

Calendar showing FPG or fasting blood glucose monitoring schedule for first 2 weeks of PIQRAY treatment 

After the first 2 weeks:
At least once every 4 weeks and as clinically indicated for the duration of treatment1

Calendar showing FPG or fasting blood glucose monitoring schedule after the first 2 weeks of PIQRAY treatment 

Test HbA1c
Once every 3 months and as clinically indicated for the duration of treatment1

 Calendar showing HbA1c monitoring schedule during PIQRAY treatment

In the SOLAR-1 study

Median time to first occurrence of grade ≥2 (FPG 160-250 mg/dL) hyperglycemia was 15 days

Median time to first occurrence of grade >2 (FPG 160-250mg/dL) hyperglycemia1

FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin.

Adjust monitoring schedule
  • Monitor fasting glucose (FPG or fasting blood glucose) as clinically indicated and at least 2x per week until fasting glucose decreases to normal levels1
Refer to PIQRAY Prescribing Information and/or the Patient Management Brochure for management recommendations and medication used in the SOLAR-1 trial
Consider consultation with a health care provider with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes1

 

FPG, fasting plasma glucose.

Adjust monitoring schedule

First 8 weeks:
Monitor fasting glucose (FPG or fasting blood glucose) at least 1x per week1

Calendar showing FPG or fasting blood glucose monitoring schedule during first 8 weeks of antihyperglycemic treatment 

After the first 8 weeks:
Monitor fasting glucose every 2 weeks and as clinically indicated1

 Calendar showing FPG or fasting blood glucose monitoring schedule after first 8 weeks of antihyperglycemic treatment


FPG, fasting plasma glucose.

References: 1. Piqray [prescribing information]. East Hanover, NJ; Novartis Pharmaceuticals Corp; 2020. 2. Data on File. Novartis Pharmaceuticals Corp; 2018. 3. Goncalves MD, Hopkins BD, Cantley LC. Phosphatidylinositol 3-kinase, growth disorders, and cancer. N Engl J Med. 2018;379(21):2052-2062.

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.