Treatment with Itovebi should be initiated by a physician experienced in the use of anticancer therapies. Patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer should be selected for treatment with Itovebi based on the presence of one or more PIK3CA mutations in a tumour or plasma specimen, whichever is available, using a CE-marked in vitro diagnostic (IVD) medical device or a validated test.
If a mutation is not detected in one specimen type, a mutation might be detected in the other specimen type, if available. Posology The recommended dose of Itovebi is 9 mg taken orally once daily with or without food. Itovebi should be administered in combination with palbociclib and fulvestrant.
The recommended dose of palbociclib is 125 mg taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. The recommended dose of fulvestrant is 500 mg administered intramuscularly on Days 1, 15, and 29, then once monthly thereafter.
Please refer to the Summary of Product Characteristics (SmPC) of palbociclib and fulvestrant for more information. Treatment of pre/perimenopausal women and men with Itovebi should also include an LHRH agonist in accordance with local clinical practice.
Duration of treatment It is recommended that patients are treated with Itovebi until disease progression or unacceptable toxicity. Delayed or missed doses Patients should be encouraged to take their dose at approximately the same time each day.
If a dose of Itovebi is missed, it can be taken within 9 hours after the time it is usually taken. After more than 9 hours, the dose should be skipped for that day. On the next day, Itovebi should be taken at the usual time. If the patient vomits after taking the Itovebi 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.
Dose modifications Management of adverse reactions may require temporary interruption, dose reduction, or discontinuation of treatment with Itovebi. The recommended dose reduction guidelines for adverse reactions are listed in Table 1.
Table 1:
Dose reduction guidelines for adverse reactions Dose level Dose and schedule Starting dose 9 mg daily First dose reduction 6 mg daily Second dose reduction 3 mg dailya a Itovebi treatment should be permanently discontinued if patients are unable to tolerate the 3 mg daily dose.
The dose of Itovebi may be re-escalated to a maximum daily dose of 9 mg based on clinical evaluation of the patient by the treating physician. Dose modification guidance for specific adverse reactions is presented in Tables 2-4. 9 mmol/L) • No adjustment of Itovebi required.
, low carbohydrate diet) and ensure adequate hydration. • Consider initiating or intensifying oral anti-hyperglycaemic treatmentb for patients with risk factors for hyperglycaemiac. 9 mmol/L). • Initiate or intensify anti-hyperglycaemic treatmentb.
• Resume Itovebi at the same dose level. 9 mmol/L) for 7 days under appropriate anti- hyperglycaemic treatment, consultation with a healthcare professional experienced in the treatment of hyperglycaemia is recommended. 8 mmol/L) • Interrupt Itovebi.
• Initiate or intensify anti-hyperglycaemic treatmentb. • Administer appropriate hydration if required. 9 mmol/L) within 7 days, resume Itovebi at the same dose level. 9 mmol/L) in ≥ 8 days, resume Itovebi at one lower dose level (see Table 1).
9 mmol/L). Resume Itovebi at one lower dose level (see Table 1). 8 mmol/L) • Interrupt Itovebi. • Initiate or intensify anti-hyperglycaemic treatmentb. • Assess for volume depletion and ketosis and administer appropriate hydration. 9 mmol/L), resume Itovebi at one lower dose level (see Table 1).
8 mmol/L) recurs within 30 days, permanently discontinue Itovebi. ULN = upper limit of normal a Fasting glucose levels (fasting plasma glucose [FPG] or fasting blood glucose [FBG]) should be checked prior to initiation of treatment.
03. b Initiate applicable anti-hyperglycaemic treatments such as metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, insulin sensitisers (such as thiazolidinediones), dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin, and review the respective prescribing information for dosing and dose titration recommendations, including local hyperglycaemia treatment guidelines.
Metformin was recommended in the INAVO120 study as the preferred initial agent. 8. 4 for risk factors for hyperglycaemia.
Stomatitis Table 3:
Dose modification and management for stomatitis Gradea Recommendation Grade 1 • No adjustment of Itovebi required. , corticosteroid-containing mouthwash) as clinically indicated. Grade 2 • Withhold Itovebi until recovery to Grade ≤ 1.
• Initiate or intensify appropriate medical therapy. Resume Itovebi at the same dose level. • For recurrent Grade 2 stomatitis, […]