Drug Detail:Piqray (Alpelisib [ al-pel-i-sib ])
Generic Name: ALPELISIB 150mg
Dosage Form: tablet
Drug Class: PI3K inhibitors
2.1 Patient Selection
Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with PIQRAY, based on the presence of one or more PIK3CA mutations in tumor tissue or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests for the detection of PIK3CA mutations in breast cancer is available at: http://www.fda.gov/CompanionDiagnostics.
2.2 Dosage and Administration
The recommended dose of PIQRAY is 300 mg (two 150 mg film-coated tablets) taken orally, once daily, with food [see Clinical Pharmacology (12.3)].
Continue treatment until disease progression or unacceptable toxicity occurs [see Dosage and Administration (2.3)].
Patients should take their dose of PIQRAY at approximately the same time each day.
Swallow PIQRAY tablets whole (tablets should not be chewed, crushed or split prior to swallowing). No tablet should be ingested if it is broken, cracked, or otherwise not intact.
If a dose of PIQRAY is missed, it can be taken with food within 9 hours after the time it is usually taken. After more than 9 hours, skip the dose for that day. The next day, take PIQRAY at the usual time.
If the patient vomits after taking the dose, advise the patient not to take an additional dose on that day, and to resume the dosing schedule the next day at the usual time.
When given with PIQRAY, the recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter. Refer to the Full Prescribing Information for fulvestrant.
2.3 Dose Modifications for Adverse Reactions
The recommended dose modifications for adverse reactions (ARs) are listed in Table 1.
| 1Only one dose reduction is permitted for pancreatitis. 2If further dose reduction below 200 mg once daily is required, discontinue PIQRAY. |
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| PIQRAY Dose Level | Dose and Schedule | Number and Strength of Tablets |
| Starting dose | 300 mg once daily | Two 150 mg tablets |
| First-dose reduction | 250 mg once daily | One 200 mg tablet and one 50 mg tablet |
| Second-dose reduction | 200 mg once daily2 | One 200 mg tablet |
Tables 2, 3, 4, and 5 summarize recommendations for dose interruption, reduction, or discontinuation of PIQRAY in the management of specific ARs.
Cutaneous Adverse Reactions
If a severe cutaneous adverse reaction (SCAR) is confirmed, permanently discontinue PIQRAY. Do not reintroduce PIQRAY in patients who have experienced previous SCAR during PIQRAY treatment [see Warnings and Precautions (5.2)].
| 1Grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 2For all grades of rash, consider consultation with a dermatologist. 3Antihistamines administered prior to rash onset may decrease incidence and severity of rash based on the SOLAR-1 trial. |
|
| [see Warnings and Precautions (5.1, 5.2)] | |
| Grade1,2 | Recommendation3 |
| Grade 1 (< 10% body surface area (BSA) with active skin toxicity) |
No PIQRAY dose adjustment required. Initiate topical corticosteroid treatment. Consider adding oral antihistamine to manage symptoms. If active rash is not improved within 28 days of appropriate treatment, add a low dose systemic corticosteroid. If the etiology is SCAR, permanently discontinue PIQRAY. |
| Grade 2 (10%-30% BSA with active skin toxicity) |
No PIQRAY dose adjustment required. Initiate or intensify topical corticosteroid and oral antihistamine treatment. Consider low dose systemic corticosteroid treatment. If rash improves to Grade ≤ 1 within 10 days, systemic corticosteroid may be discontinued. If the etiology is SCAR, permanently discontinue PIQRAY. |
| Grade 3 (e.g., severe rash not responsive to medical management) (> 30% BSA with active skin toxicity) |
Interrupt PIQRAY. Initiate or intensify topical/systemic corticosteroid and oral antihistamine treatment. If the etiology is SCAR, permanently discontinue PIQRAY. If the etiology is not a SCAR, interrupt dose until improvement to Grade ≤ 1, then resume PIQRAY at next lower dose level. |
| Grade 4 (e.g., severe bullous, blistering or exfoliating skin conditions) (any % BSA associated with extensive superinfection, with IV antibiotics indicated; life-threatening consequences) |
Permanently discontinue PIQRAY. |
Hyperglycemia
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. In patients with risk factors for hyperglycemia, monitor fasting glucose more closely and as clinically indicated [see Warnings and Precautions (5.3)].
| Abbreviation: ULN, upper limit of normal. 1FPG/Fasting Blood Glucose/Grade levels reflect hyperglycemia grading according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. 2Initiate applicable anti-hyperglycemic medications, including metformin, SGLT2 inhibitors or insulin sensitizers (such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors), and review respective prescribing information for dosing and dose titration recommendations, including local hyperglycemic treatment guidelines. Metformin was recommended in the SOLAR-1 trial with the following guidance: Initiate metformin 500 mg once daily. Based on tolerability, metformin dose may be increased to 500 mg twice daily, followed by 500 mg with breakfast, and 1,000 mg with dinner, followed by further increase to 1,000 mg twice daily if needed [see Warnings and Precautions (5.3)]. 3As recommended in the SOLAR-1 trial, insulin may be used for 1-2 days until hyperglycemia resolves. However, this may not be necessary in the majority of PIQRAY-induced hyperglycemia, given the short half-life of PIQRAY and the expectation of glucose levels normalizing after interruption of PIQRAY. |
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| [see Warnings and Precautions (5.3)] | |
| Fasting Plasma Glucose (FPG)/Fasting Blood Glucose Values1 | Recommendation |
| Dose modifications and management should only be based on fasting glucose values (FPG or fasting blood glucose). | |
| Grade 1 Fasting glucose > ULN -160 mg/dL or > ULN -8.9 mmol/L |
No PIQRAY dose adjustment required. Initiate or intensify anti-hyperglycemic treatment2. |
| Grade 2 Fasting glucose > 160-250 mg/dL or > 8.9-13.9 mmol/L |
No PIQRAY dose adjustment required. Initiate or intensify anti-hyperglycemic treatment2. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 mmol/L within 21 days under appropriate anti-hyperglycemic treatment2,3, reduce PIQRAY dose by 1 dose level and follow fasting glucose value specific recommendations. |
| Grade 3 > 250-500 mg/dL or > 13.9-27.8 mmol/L |
Interrupt PIQRAY. Initiate or intensify oral anti-hyperglycemic treatment2 and consider additional anti-hyperglycemic medications3 for 1-2 days until hyperglycemia improves, as clinically indicated. Administer intravenous hydration and consider appropriate treatment (e.g., intervention for electrolyte/ketoacidosis/hyperosmolar disturbances). If fasting glucose decreases to ≤ 160 mg/dL or 8.9 mmol/L within 3 to 5 days under appropriate anti-hyperglycemic treatment, resume PIQRAY at 1 lower dose level. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 mmol/L within 3 to 5 days under appropriate anti-hyperglycemic treatment, consultation with a physician with expertise in the treatment of hyperglycemia is recommended. If fasting glucose does not decrease to ≤ 160 mg/dL or 8.9 mmol/L within 21 days following appropriate anti-hyperglycemic treatment2,3, permanently discontinue PIQRAY treatment. |
| Grade 4 > 500 mg/dL or > 27.8 mmol/L |
Interrupt PIQRAY. Initiate or intensify appropriate anti-hyperglycemic treatment2,3 (administer intravenous hydration and consider appropriate treatment (e.g., intervention for electrolyte/ketoacidosis/hyperosmolar disturbances)), re-check fasting glucose within 24 hours and as clinically indicated. If fasting glucose decreases to ≤ 500 mg/dL or 27.8 mmol/L, follow fasting glucose value-specific recommendations for Grade 3. If fasting glucose is confirmed at > 500 mg/dL or 27.8 mmol/L, permanently discontinue PIQRAY treatment. |
Diarrhea or Colitis
| 1Grading according to CTCAE Version 5.0. 2For Grade 2 and 3 colitis, consider additional treatment, such as enteric-acting and/or systemic steroids. |
|
| [see Warnings and Precautions (5.5)] | |
| Grade1 | Recommendation |
| Grade 1 | No PIQRAY dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. |
| Grade 2 | Interrupt PIQRAY dose until improvement to Grade ≤ 1, then resume PIQRAY at the same dose level. For recurrent Grade ≥ 2, interrupt PIQRAY dose until improvement to Grade ≤ 1, then resume PIQRAY at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated2. |
| Grade 3 | Interrupt PIQRAY dose until improvement to Grade ≤ 1, then resume PIQRAY at the next lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated2. |
| Grade 4 | Permanently discontinue PIQRAY. |
Other Toxicities
| 1Grading according to CTCAE Version 5.0. 2For Grade 2 and 3 pancreatitis, interrupt PIQRAY dose until improvement to Grade < 2 and resume at next lower-dose level. Only one dose reduction is permitted. If toxicity reoccurs, permanently discontinue PIQRAY treatment. 3For Grade 2 total bilirubin elevation, interrupt PIQRAY dose until improvement to Grade ≤ 1 and resume at the same dose if resolved in ≤ 14 days or resume at the next lower dose level if improved in > 14 days. |
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| Grade1 | Recommendation |
| Grade 1 or 2 | No PIQRAY dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated2,3. |
| Grade 3 | Interrupt PIQRAY dose until improvement to Grade ≤ 1, then resume PIQRAY at the next lower dose level. |
| Grade 4 | Permanently discontinue PIQRAY. |
Refer to the Full Prescribing Information of fulvestrant for dose modification guidelines in the event of toxicity and for other relevant safety information.
