In combination with fulvestrant for patients with HR+/HER2− aBC or mBC with PIK3CA, AKT1, or PTEN alterations following progression on or after ET ± CDK4/6i
Adverse Reactions
Adverse reactions were mostly Grade 1 or 21*
ARs in ≥10% (all Grades) of patients
| Adverse reactions | TRUQAP + fulvestrant (n=155) | Placebo + fulvestrant (n=133) | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Gastrointestinal disorders | ||||
| Diarrhea | 77 | 12 | 19 | 0.8 |
| Nausea | 35 | 1.3 | 14 | 0.8 |
| Stomatitis† | 25 | 1.9 | 5 | 0 |
| Vomiting | 21 | 1.9 | 7 | 0.8 |
| Skin and subcutaneous tissue disorders | ||||
| Cutaneous adverse reactions‡ | 56 | 15 | 16 | 0.8 |
| General disorders and administration site conditions | ||||
| Fatigue† | 38 | 1.9 | 27 | 1.5 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 17 | 0 | 8 | 0.8 |
| Nervous system disorders | ||||
| Headache† | 17 | 0 | 13 | 0.8 |
| Infections and infestations | ||||
| Urinary tract infections† | 14 | 0.6 | 5 | 0 |
| Renal and urinary disorders | ||||
| Renal injury§ | 11 | 2.6 | 1.5 | 0.8 |
Other clinically relevant ARs reported in less than 10% of patients in the TRUQAP + fulvestrant group included:
- Anemia, hypersensitivity (including anaphylactic reaction), dysgeusia, dyspepsia, pneumonia, and pyrexia
In CAPItello-291, patients did not receive primary prophylaxis for diarrhea, rash, or hyperglycemia2
CAPItello-291 allowed for patients with HbA1C <8% and diabetes not requiring insulin1
Laboratory Abnormalities
Laboratory abnormalities (≥10% of patients) that worsened from baseline1
| Laboratory abnormality | TRUQAP + fulvestrant* | Placebo + fulvestrant† | ||
|---|---|---|---|---|
| All Grades (%) | Grade 3-4 (%) | All Grades (%) | Grade 3-4 (%) | |
| Glucose metabolism | ||||
| Increased random glucose | 58 | 9 | 17 | 0 |
| Increased fasting glucose | 37 | 0.6 | 29 | 0 |
| Hematology | ||||
| Decreased lymphocytes | 49 | 11 | 14 | 2.3 |
| Decreased hemoglobin | 47 | 2 | 22 | 2.3 |
| Decreased leukocytes | 35 | 0.6 | 23 | 0 |
| Decreased neutrophils | 25 | 1.9 | 16 | 0.8 |
| Decreased platelets | 12 | 1.9 | 6 | 0.8 |
| Other | ||||
| Increased triglycerides | 30 | 0.7 | 22 | 0.9 |
| Increased alanine aminotransferase | 23 | 2.6 | 13 | 0 |
| Electrolytes/Renal | ||||
| Decreased corrected calcium | 19 | 0.6 | 8 | 0 |
| Increased creatinine | 19 | 1.3 | 4.6 | 0.8 |
| Decreased potassium | 17 | 4.5 | 8 | 0 |
Rates of Dose Adjustments
Rates of dose discontinuation/reduction due to ARs1
TRUQAP discontinuation due to ARs occurred in 10% of patients
- The most frequent (≥2%) AR leading to discontinuation was cutaneous adverse reactions (6%)
Dose reductions due to ARs occurred in 21% of patients receiving TRUQAP + fulvestrant
- The most frequent (≥2%) ARs leading to dose reduction were diarrhea and cutaneous adverse reactions (8% each)
Had a low rate of discontinuation due to ARs (10%)
NCCN
CATEGORY 1 PREFERRED
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer recommends capivasertib (TRUQAP®) + fulvestrant as a Category 1 Preferred treatment option for HR+/HER2− aBC or mBC with at least one or more PIK3CA or AKT1 activating mutations or PTEN alterations following progression after one or more prior lines of ET, including one line containing a CDK4/6i3
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IMPORTANT SAFETY INFORMATION ABOUT TRUQAP® (capivasertib) tablets
TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components.
Hyperglycemia
Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, can occur in patients treated with TRUQAP (n=355).
Increased fasting glucose (FG) from baseline occurred in 37% of patients treated with TRUQAP, including 11% of patients with Grade 2 (FG >160 to 250 mg/dL), 2% with Grade 3 (FG >250 to 500 mg/dL), and 1.1% with Grade 4 (FG >500 mg/dL) events. The median time to first occurrence of hyperglycemia was 15 days (range: 1 to 367). Dose reduction for hyperglycemia was required in 0.6% of patients and permanent discontinuation was required in 0.6% of patients. Diabetic ketoacidosis occurred in 0.3% of patients and diabetic metabolic decompensation in 0.6% of patients.
In CAPItello-291, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication either initiated or changed during the study, including treatment with insulin in 4.8% (17/355) of patients.
The safety of TRUQAP has not been established in patients with Type I diabetes or diabetes requiring insulin. Patients with insulin-dependent diabetes were excluded from CAPItello-291.
Before initiating treatment with TRUQAP, test fasting glucose levels (fasting plasma glucose or fasting blood glucose), hemoglobin A1C (HbA1C) levels, and optimize fasting glucose. After initiating treatment with TRUQAP, monitor or self-monitor FG levels on Day 3 or 4 of the dosing week during weeks 1, 2, 4, 6, and 8; then monthly while on treatment with TRUQAP; and as clinically indicated. Monitor HbA1C levels every 3 months during treatment with TRUQAP and as clinically indicated. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of FG levels.
For patients who experience hyperglycemia during treatment with TRUQAP, monitor FG at least twice weekly, on days on and off TRUQAP, until FG decreases to baseline levels. During treatment with anti-diabetic medications, monitor FG at least once a week for 2 months, followed by once every 2 weeks, or as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and initiation of FG monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients on the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes.
Withhold TRUQAP immediately when ketoacidosis is suspected. If ketoacidosis is confirmed, permanently discontinue TRUQAP. Based on the severity of hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP.
Diarrhea
Severe diarrhea associated with dehydration occurred in patients who received TRUQAP (n=355).
Diarrhea occurred in 72% of patients. Grade 3 or 4 diarrhea occurred in 9% of patients. The median time to first occurrence was 8 days (range: 1 to 519). In the 257 patients with diarrhea, 59% required antidiarrheal medications to manage symptoms. Dose reductions were required in 8% of patients and 2% of patients permanently discontinued TRUQAP due to diarrhea. In patients with Grade ≥2 diarrhea (n=93) with at least 1 grade improvement (n=89), median time to improvement from the first event was 4 days (range: 1 to 154).
Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity.
Cutaneous Adverse Reactions
Cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia, and drug reaction with eosinophilia and systemic symptoms (DRESS), occurred in patients who received TRUQAP (n=355).
Cutaneous adverse reactions occurred in 58% of patients. Grade 3 or 4 cutaneous adverse reactions occurred in 17% of patients receiving TRUQAP. EM occurred in 1.7% of patients and DRESS occurred in 0.3% of patients. Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions.
Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, dose reduce, or permanently discontinue TRUQAP based on severity.
Embryo-Fetal Toxicity
Based on findings from animals and mechanism of action, TRUQAP 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 TRUQAP and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose.
TRUQAP is used in combination with fulvestrant. Refer to the full Prescribing Information of fulvestrant for pregnancy and contraception information.
ADVERSE REACTIONS
Among the 355 patients who received TRUQAP in CAPItello-291, the most common (≥20%) adverse reactions, including laboratory abnormalities, were diarrhea (72%), cutaneous adverse reactions (58%), increased random glucose (57%), decreased lymphocytes (47%), decreased hemoglobin (45%), increased fasting glucose (37%), nausea and fatigue (35% each), decreased leukocytes (32%), increased triglycerides (27%), decreased neutrophils (23%), increased creatinine (22%), vomiting (21%), and stomatitis (20%).
In the 155 patients with PIK3CA/AKT1/PTEN alterations treated with TRUQAP + fulvestrant, dose reductions due to adverse reactions were reported in 21% of patients. Permanent TRUQAP discontinuation due to an adverse reaction occurred in 10% of patients. Dose interruptions of TRUQAP occurred in 39% of patients.
DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid concomitant use with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the dose of TRUQAP and monitor patients for adverse reactions.
Moderate CYP3A Inhibitors: When concomitantly used with a moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions.
Strong or Moderate CYP3A Inducers: Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers.
INDICATION AND USAGE
TRUQAP in combination with fulvestrant is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alteration as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.
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INDICATION AND USAGE
TRUQAP in combination with fulvestrant is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alteration as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.
