Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: AstraZeneca AB, SE-151 85 Södertälje, Sweden
TRUQAP is indicated in combination with fulvestrant for the treatment of adult patients with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine-based regimen (see section 5.1).
In pre- or perimenopausal women, TRUQAP plus fulvestrant should be combined with a luteinising hormone releasing hormone (LHRH) agonist.
For men, administration of LHRH agonist according to current clinical practice standards should be considered.
Treatment with TRUQAP should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Patients with ER-positive, HER2-negative advanced breast cancer should be selected for treatment with TRUQAP based on the presence of one or more PIK3CA/AKT1/PTEN -alterations which should be assessed by a CE-marked IVD with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used.
The recommended dose of TRUQAP is 400 mg (two 200 mg tablets) twice daily, approximately 12 hours apart (total daily dose of 800 mg), for 4 days followed by 3 days off treatment. See Table 1.
Table 1. TRUQAP dosing schedule for each week:
| Day | 1 | 2 | 3 | 4 | 5* | 6* | 7* |
| Morning | 2 × 200 mg | 2 × 200 mg | 2 × 200 mg | 2 × 200 mg | - | - | - |
| Evening | 2 × 200 mg | 2 × 200 mg | 2 × 200 mg | 2 × 200 mg | - | - | - |
* No dosing on day 5, 6 and 7.
TRUQAP should be co-administered with fulvestrant. The recommended dose of fulvestrant is 500 mg administered on Days 1, 15, and 29, and once monthly thereafter. Refer to the Summary of Product Characteristics (SmPC) of fulvestrant for more information.
If a dose of TRUQAP is missed, it can be taken within 4 hours after the time it is usually taken. After more than 4 hours, the dose should be skipped. The next dose of TRUQAP should be taken at the usual time. There should be at least 8 hours between doses.
If the patient vomits, an additional dose should not be taken. The next dose of TRUQAP should be taken at the usual time.
Treatment with capivasertib should continue until disease progression or unacceptable toxicity occurs.
Treatment with TRUQAP may be interrupted to manage adverse reactions and dose reduction can be considered. Dose reductions for TRUQAP should be carried out as described in Table 2. The dose of capivasertib can be reduced up to two times. Dose modification guidance for specific adverse reactions is presented in Tables 3-5.
Table 2. TRUQAP dose reduction guidelines for adverse reactions:
| TRUQAP | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Starting dose | 400 mg twice daily for 4 days followed by 3 days off treatment | Two 200 mg tablets twice daily |
| First dose reduction | 320 mg twice daily for 4 days followed by 3 days off treatment | Two 160 mg tablets twice daily |
| Second dose reduction | 200 mg twice daily for 4 days followed by 3 days off treatment | One 200 mg tablet twice daily |
Table 3. Recommended dose modification for TRUQAP for hyperglycaemia:
| CTCAE Gradea and fasting glucose (FG)b values prior to TRUQAP dose | Recommendationc |
|---|---|
| Grade 1 ˃ ULN-160 mg/dL or ˃ ULN-8.9 mmol/L or HbA1C ˃ 7% | No TRUQAP dose adjustment required. Consider initiation or intensification of oral anti-diabetic treatmentd. |
| Grade 2 ˃ 160-250 mg/dL or ˃ 8.9-13.9 mmol/L | Withhold TRUQAP and initiate or intensify oral anti-diabetic treatment. If improvement to ≤ 160 mg/dL (or ≤ 8.9 mmol/L) is reached within 28 days, restart TRUQAP at the same dose level and maintain initiated or intensified anti-diabetic treatment. If improvement to ≤ 160 mg/dL (or ≤ 8.9 mmol/L) is reached after 28 days, restart TRUQAP at one lower dose level and maintain initiated or intensified anti-diabetic treatment. |
| Grade 3 ˃ 250-500 mg/dL or ˃ 13.9-27.8 mmol/L | Withhold TRUQAP and consult a diabetologist. Initiate or intensify oral anti-diabetic treatment. Consider additional anti-diabetic medicinal products such as insuline, as clinically indicated. Consider intravenous hydration and provide appropriate clinical management as per local guidelines. If FG decreases to ≤ 160 mg/dL (or ≤ 8.9 mmol/L) within 28 days, restart TRUQAP at one lower dose level and maintain initiated or intensified anti- diabetic treatment. If FG does not decrease to ≤ 160 mg/dL (or ≤ 8.9 mmol/L) within 28 days following appropriate treatment permanently discontinue TRUQAP. |
| Grade 4 ˃ 500 mg/dL or ˃ 27.8 mmol/L | Withhold TRUQAP and consult with a diabetologist. Initiate or intensify appropriate anti-diabetic treatment. Consider insuline, (dosing and duration as clinically indicated), intravenous hydration and provide appropriate clinical management as per local guidelines. If FG decreases to ≤ 500 mg/dL (or ≤ 27.8 mmol/L) within 24 hours, then follow the guidance in the table for the relevant grade. If FG is confirmed at ˃ 500 mg/dL (or ˃ 27.8 mmol/L) after 24 hours, permanently discontinue TRUQAP treatment. |
a Grading according to NCI CTCAE Version 4.03.
b Considerations should be also given to increases in HbA1C.
c See section 4.4 for further recommendations on monitoring of glycaemia and other metabolic parameters.
d Consultation with a diabetologist should be considered when selecting the anti-diabetic medicinal product. A potential for hypoglycaemia with anti-diabetic medicinal product administration on non-TRUQAP dosing days should be taken into account. Patients should also consider consultation with a dietician to make lifestyle changes that may reduce hyperglycaemia (see section 4.4).
Metformin is currently the preferred oral antidiabetic recommended for the management of hyperglycaemia occurring in patients participating in studies of capivasertib. Dosing and management of patients receiving the metformin and capivasertib combination requires caution. Due to the potential interaction of metformin and capivasertib (caused by the inhibition of renal transporters [e.g. OCT2] involved in the excretion of metformin), when taking both capivasertib and metformin concurrently, it is recommended weekly monitoring of creatinine after initiation of metformin, for up to 3 weeks and then on Day 1 of each cycle thereafter.
Metformin should only be given on the days when capivasertib is also administered (the half-life of capivasertib is approximately 8 hours) and should be withdrawn when treatment with capivasertib is withdrawn, unless otherwise clinically indicated.
e There is limited experience in patients receiving insulin when being treated with TRUQAP.
Secondary prophylaxis should be considered in patients with recurrent diarrhoea (see section 4.4).
Table 4. Recommended dose modification for TRUQAP for diarrhoea:
| CTCAE Gradea | Recommendation |
|---|---|
| Grade 1 | No TRUQAP dose adjustment required. Initiate appropriate anti-diarrhoeal therapy, maximise supportive care and monitor as clinically indicated. |
| Grade 2 | Initiate or intensify appropriate anti-diarrhoeal treatment, monitor the patient and if clinically indicated interrupt TRUQAP dose for up to 28 days until recovery to ≤ Grade 1 and resume TRUQAP dosing at same dose, or one lower dose level as clinically indicated. If Grade 2 diarrhoea is persistent or recurring, maintain appropriate medical therapy and restart TRUQAP at the next lower dose level, as clinically indicated. |
| Grade 3 | Interrupt TRUQAP. Initiate or intensify appropriate anti-diarrhoeal treatment and monitor as clinically indicated. If the symptoms improve to ≤ Grade 1 in 28 days resume TRUQAP at one lower dose level. If the symptom does not improve to ≤ Grade 1 in 28 days permanently discontinue TRUQAP. |
| Grade 4 | Permanently discontinue TRUQAP. |
a Grade according to the NCI CTCAE Version 5.0.
Consultation with a dermatologist for all grades of skin drug reactions regardless of the severity should be considered. In patients with persistent rash and/or previous occurrence of grade 3 rash, secondary prophylaxis should be considered by continuing oral antihistamines and/or topical steroids (see section 4.4).
Table 5. Recommended dose modification for TRUQAP for rash and other skin drug reactions:
| CTCAE Gradea | Recommendation |
|---|---|
| Grade 1 | No TRUQAP dose adjustment required. Initiate emollients and consider adding oral non-sedating antihistamine treatment as clinically indicated to manage symptoms. |
| Grade 2 | Initiate or intensify topical steroid treatment and consider non-sedating oral antihistamines. If no improvement with treatment, interrupt TRUQAP. Resume at the same dose level once the rash becomes clinically tolerable. |
| Grade 3 | Interrupt TRUQAP. Initiate appropriate dermatological treatment with topical steroid of moderate/higher strength, non-sedating oral antihistamines and/or systemic steroids. If symptoms improve within 28 days to ≤ Grade 1, restart TRUQAP on one lower dose level. If the symptoms do not improve to ≤ Grade 1 in 28 days discontinue TRUQAP. In patients with reoccurrence of intolerable ≥ Grade 3 rash, consider permanent discontinuation of TRUQAP. |
| Grade 4 | Permanently discontinue TRUQAP. |
a Grading according to CTCAE Version 5.0.
Table 6. Recommended dose modification and management for other toxicities (excluding hyperglycaemia, diarrhoea, rash and other skin drug reactions):
| CTCAE Gradea | Recommendation |
|---|---|
| Grade 1 | No TRUQAP dose adjustment required, initiate appropriate medical therapy and monitor as clinically indicated. |
| Grade 2 | Interrupt TRUQAP until symptoms improve to ≤ Grade 1. |
| Grade 3 | Interrupt TRUQAP until symptoms improve to ≤ Grade 1. If symptoms improve, restart TRUQAP at same dose or one lower dose level as clinically appropriate. |
| Grade 4 | Permanently discontinue TRUQAP. |
a Grading according to CTCAE Version 5.0.
Co-administration of TRUQAP with strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, the dose of TRUQAP should be reduced to 320 mg twice daily (equivalent to a total daily dose of 640 mg).
TRUQAP dose should be reduced to 320 mg twice daily (equivalent to a total daily dose of 640 mg) when co-administered with moderate CYP3A4 inhibitors.
After discontinuation of a strong or moderate CYP3A4 inhibitor, TRUQAP dosage (after 3 to 5 half-lives of the inhibitor) that was taken prior to initiating the strong or moderate CYP3A4 inhibitor should be resumed.
See section 4.5 for further information.
No dose adjustment is required for elderly patients (see section 5.2). There are limited data in patients aged ≥75 years.
No dose adjustment is required for patients with mild or moderate renal impairment. TRUQAP is not recommended for patients with severe renal impairment, as safety and pharmacokinetics have not been studied in these patients (see section 5.2).
No dose adjustment is required for patients with mild hepatic impairment. Limited data are available for patients with moderate hepatic impairment; TRUQAP should be administered to patients with moderate hepatic impairment only if the benefit outweighs the risk and these patients should be monitored closely for signs of toxicity. TRUQAP is not recommended for patients with severe hepatic impairment, as safety and pharmacokinetics have not been studied in these patients (see section 5.2).
The safety and efficacy of TRUQAP in children aged 0-18 years of age has not been established. No data are available.
TRUQAP is for oral use. The tablets can be taken with or without food (see section 5.2). They should be swallowed whole with water and not chewed, crushed, dissolved, or divided. No tablet should be ingested if it is broken, cracked, or otherwise not intact because these methods have not been studied in clinical trials.
There is currently no specific treatment in the event of an overdose with TRUQAP. Higher than the indicated dosing of capivasertib can increase risk of capivasertib adverse reactions, including diarrhoea. Physicians should follow general supportive measures and patients should be treated symptomatically.
4 years.
The medicinal product does not require any special storage conditions.
Aluminium/Aluminium blister containing 16 film-coated tablets. Pack of 64 tablets (4 blisters).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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