Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
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, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy (see section 5.1).
Treatment with Piqray should be initiated by a physician experienced in the use of anticancer therapies.
Patients with HR-positive, HER2-negative advanced breast cancer should be selected for treatment with Piqray based on the presence of a PIK3CA mutation in tumour or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, tumour tissue should be tested if available.
The recommended dose is 300 mg alpelisib (2x 150 mg film-coated tablets) taken once daily on a continuous basis. Piqray should be taken immediately after food, at approximately the same time each day (see section 5.2). The maximum recommended daily dose of Piqray is 300 mg.
If a dose of Piqray is missed, it can be taken immediately following food and within 9 hours after the time it is usually administered. After more than 9 hours, the dose should be skipped for that day. On the next day, Piqray should be taken at the usual time. If the patient vomits after taking the Piqray dose, the patient should not take an additional dose on that day and should resume the usual dosing schedule the next day at the usual time.
Piqray should be co-administered with fulvestrant. The recommended dose of fulvestrant is 500 mg administered intramuscularly on days 1, 15 and 29, and once monthly thereafter. Please refer to the full prescribing information of fulvestrant.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Dose modifications may be necessary to improve tolerability.
Management of severe or intolerable adverse drug reactions (ADRs) may require temporary dose interruption, reduction, and/or discontinuation of Piqray. If dose reduction is required, the dose reduction guidelines for ADRs are listed in Table 1. A maximum of 2 dose reductions are recommended, after which the patient should be permanently discontinued from treatment with Piqray. Dose reduction should be based on the worst preceding toxicity.
Table 1. Recommended dose reduction guidelines for ADRs for Piqray1:
| Piqray dose level | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Starting dose | 300 mg/day continuously | 2x 150 mg tablets |
| First dose reduction | 250 mg/day continuously | 1x 200 mg tablet and 1x 50 mg tablet |
| Second dose reduction | 200 mg/day continuously | 1x 200 mg tablet |
1 Only one dose reduction is permitted for pancreatitis.
Tables 2-5 summarise the recommendations for dose interruption, reduction or discontinuation of Piqray in the management of specific ADRs. The clinical judgement of the treating physician, including confirmation of laboratory values if deemed necessary, should guide the management plan of each patient based on the individual benefit/risk assessment for treatment with Piqray.
Consultation with a healthcare professional experienced in the treatment of hyperglycaemia should always be considered and is recommended for patients who are pre-diabetic or those with fasting glucose (FG) >250 mg/dl or 13.9 mmol/l, body mass index (BMI) ≥30 or age ≥75 years.
Consultation with a diabetologist or a healthcare professional experienced in the treatment of hyperglycaemia should always take place for patients with diabetes.
Table 2. Dose modification and management for hyperglycaemia:
| Fasting glucose (FG) values1 | Recommendation |
|---|---|
| Dose modification and management should only be based on fasting glucose (plasma/blood) values. | |
| >ULN-160 mg/dl or >ULN-8.9 mmol/l | No Piqray dose adjustment required. Initiate or intensify oral antidiabetic treatment2. |
| >160-250 mg/dl or >8.9-13.9 mmol/l | No Piqray dose adjustment required. Initiate or intensify oral antidiabetic treatment2. If FG does not decrease to ≤160 mg/dl or 8.9 mmol/l within 21 days with appropriate oral antidiabetic treatment2,3, reduce Piqray dose by 1 dose level and follow FG-value-specific recommendations. |
| >250-500 mg/dl or >13.9-27.8 mmol/l | Interrupt Piqray. Initiate or intensify oral antidiabetic treatment2 and consider additional antidiabetic medicinal products such as insulin3 for 1-2 days until hyperglycaemia resolves, as clinically indicated. Administer intravenous hydration and consider appropriate treatment (e.g. intervention for electrolyte / ketoacidosis / hyperosmolar disturbances). If FG decreases to ≤160 mg/dl or 8.9 mmol/l within 3 to 5 days under appropriate antidiabetic treatment, resume Piqray at next lower dose level. If FG does not decrease to ≤160 mg/dl or 8.9 mmol/l within 3 to 5 days under appropriate antidiabetic treatment, consultation with a healthcare professional with expertise in the treatment of hyperglycaemia is recommended. If FG does not decrease to ≤160 mg/dl or 8.9 mmol/l within 21 days following appropriate antidiabetic treatment2,3, permanently discontinue Piqray treatment. |
| >500 mg/dl or >27.8 mmol/l | Interrupt Piqray. Initiate or intensify appropriate antidiabetic treatment2,3 (administer intravenous hydration and consider appropriate treatment [e.g. intervention for electrolyte / ketoacidosis / hyperosmolar disturbances]), re-check within 24 hours and as clinically indicated. If FG decreases to ≤500 mg/dl or ≤27.8 mmol/l, then follow FG-value-specific recommendations for <500 mg/dl. If FG is confirmed at >500 mg/dl or >27.8 mmol/l after 24 hours, permanently discontinue Piqray treatment. |
1 Fasting glucose levels reflect hyperglycaemia grading according to CTCAE Version 4.03 CTCAE = Common Terminology Criteria for Adverse Events.
2 Applicable antidiabetic medicinal products, such as metformin, SGLT2 inhibitors or insulin sensitisers (such as thiazolidinediones or dipeptidyl peptidase-4 inhibitors), should be initiated and the respective prescribing information should be reviewed for dosing and dose titration recommendations, including local diabetic treatment guidelines. Metformin was recommended in the phase III clinical study with the following guidance: Metformin should be initiated at 500 mg once daily. Based on tolerability, the metformin dose may be increased to 500 mg twice daily, followed by 500 mg with breakfast, and 1 000 mg with the evening meal, followed by further increase to 1 000 mg twice daily if needed (see section 4.4).
3 As recommended in the phase III clinical study, insulin may be used for 1-2 days until hyperglycaemia resolves. However, this may not be necessary in the majority of cases of alpelisib-induced hyperglycaemia, given the short half-life of alpelisib and the expectation that glucose levels will normalise following interruption of Piqray.
Baseline diabetic and pre-diabetic status, baseline BMI ≥30 and baseline age ≥75 years have been found to be risk factors for hyperglycaemia in patients treated with alpelisib. These risk factors were present in 74.7% of patients with any grade of hyperglycaemia and in 86.2% of patients with grade 3 or 4 hyperglycaemia (see section 4.4).
Oral antihistamine administration may be considered prophylactically, at the time of initiation of treatment with Piqray. Additionally, antihistamines are recommended to manage symptoms of rash.
Topical corticosteroid treatment should be initiated at the first signs of rash and systemic corticosteroids should be considered for moderate to severe rashes. Based on the severity of rash, Piqray may require dose interruption, reduction or discontinuation as described in Table 3 (see section 4.8).
Table 3. Dose modification and management for rash:
| Grade1 | Recommendation |
|---|---|
| }All grades | Consultation with a dermatologist should always be considered. |
| Grade 1 (<10% body surface area [BSA] with active skin toxicity) | No Piqray dose adjustment required. Initiate topical corticosteroid treatment. Consider adding oral antihistamine treatment to manage symptoms. If active rash is not improved within 28 days of appropriate treatment, add a low dose systemic corticosteroid. |
| 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. |
| Grade 3 (e.g. severe rash not responsive to medical management) (>30% BSA with active skin toxicity) | Interrupt Piqray until rash improves to grade ≤1. Initiate or intensify topical/systemic corticosteroid and antihistamine treatment. Once rash improves to grade ≤1, 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 intravenous antibiotics indicated; life-threatening consequences) | Permanently discontinue Piqray. |
1 Grading according to CTCAE Version 5.0
Table 4. Dose modification and management for diarrhoea or colitis:
| Grade1 | Recommendation |
|---|---|
| Grade 1 | No Piqray dose adjustment is required. Initiate appropriate medical therapy and monitor as clinically indicated. |
| Grade 22 | Interrupt Piqray dose. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. If diarrhoea or colitis improves to grade ≤1, then resume Piqray at same dose level. For recurrent diarrhoea or colitis grade ≥2, interrupt Piqray dose until improvement to grade ≤1, then resume Piqray at the next lower dose level. |
| Grade 32,3 | Interrupt Piqray dose. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. If diarrhoea or colitis improves to grade ≤1, then resume Piqray at the next lower dose level. |
| Grade 42,3 | Permanently discontinue Piqray. |
1 Grading according to CTCAE Version 5.0.
2 For grade ≥2 consider additional treatment, such as steroids.
3 Patients should additionally be managed according to local standard of care, including electrolyte monitoring, administration of antiemetics and antidiarrhoeal medicinal products and/or fluid replacement and electrolyte supplements, as clinically indicated.
Table 5. Dose modification and management for other toxicities (excluding hyperglycaemia, rash and diarrhoea or colitis):
| Grade1 | Recommendation |
|---|---|
| Grade 1 or 2 | No Piqray dose adjustment 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 level2. |
| Grade 4 | Permanently discontinue Piqray3. |
1 Grading according to CTCAE Version 5.0
2 For grade 2 and 3 pancreatitis, interrupt Piqray dose until improvement to grade ≤1 and resume at next lower dose level. Only one dose reduction is permitted. If toxicity recurs, permanently discontinue Piqray treatment.
3 For grade 2 total bilirubin elevation, interrupt Piqray dose until recovery to grade ≤1 and resume at the same dose if resolved in ≤14 days or resume at the next lower dose level if resolved in >14 days.
No dose regimen adjustment is required in patients aged 65 years or above (see section 5.2). There are limited data in patients aged ≥75 years, and especially for those ≥85 years.
Based on population pharmacokinetic analysis, no dose adjustment is necessary in patients with mild or moderate renal impairment (see section 5.2). Caution should be used in patients with severe renal impairment as there is no experience with Piqray in this population.
Based on a hepatic impairment study in non-cancer subjects with impaired hepatic function, no dose adjustment is necessary in patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B or C, respectively) (see section 5.2).
The safety and efficacy of Piqray in children aged 0-18 years have not been established. No data are available.
Piqray is for oral use. The tablets should be swallowed whole. They should not be chewed, crushed or split prior to swallowing. Tablets that are broken, cracked or otherwise not intact should not be ingested.
The adverse reactions associated with overdose have been consistent with the safety profile of Piqray and included hyperglycaemia, nausea, asthenia and rash.
General symptomatic and supportive measures should be initiated in all cases of overdose where necessary. There is no known antidote for Piqray.
3 years.
This medical product does not require any special storage conditions.
PVC/PCTFE/alu (polyvinylchloride/polychlorotrifluoroethylene/aluminium) blister sealed into a blister card containing 14 film-coated tablets.
Piqray 50 mg and 200 mg film-coated tablets:
Packs containing 28 film-coated tablets (14 of 50 mg and 14 of 200 mg) or 56 film-coated tablets (28 of 50 mg and 28 of 200 mg).
Multipacks containing 168 film-coated tablets (3x 56, each comprising 28 tablets of 50 mg and 28 tablets of 200 mg).
Piqray 150 mg film-coated tablets:
Packs containing 28 or 56 film-coated tablets.
Multipacks containing 168 (3x 56) film-coated tablets.
Piqray 200 mg film-coated tablets:
Packs containing 14 or 28 film-coated tablets.
Multipacks containing 84 (3x 28) film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
