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
Trial Design
In combination with fulvestrant,
TRUQAP was studied in a global, phase 3, randomized, double-blind, multicenter trial with 70% of patients having prior CDK4/6i1,2
CAPItello-291 (N=708)1*
Dual primary endpoints1
- PFS in overall population (investigator assessed)
- PFS in patients with PIK3CA/AKT1/PTEN alterations (investigator assessed)
Key secondary endpoints1
- Overall survival
- ORR (investigator assessed)
- Safety
- DoR
- Pathway alteration status was determined centrally using next-generation sequencing in tumor tissue with the FoundationOne®CDx assay. Patients were treated until disease progression or unacceptable toxicity.1
- *Overall population (N=708); PIK3CA/AKT1/PTEN-altered population (n=289; TRUQAP + fulvestrant n=155; placebo + fulvestrant n=134).1
- †Region 1: United States, Canada, Western Europe, Australia, and Israel; Region 2: Latin America, Eastern Europe, and Russia; Region 3: Asia.1
Baseline Characteristics
In CAPItello-291,
Baseline characteristics were balanced between treatment arms2
In patients with PIK3CA, AKT1, or PTEN alterations
| Baseline characteristics | TRUQAP + fulvestrant (n=155) | Placebo + fulvestrant (n=134) |
|---|---|---|
| Median age, years (range) | 58 (36-84) | 60 (34-90) |
| Female, n (%) | 153 (98.7) | 134 (100) |
| Postmenopausal, n (%) | 130 (83.9) | 105 (78.4) |
| Race, n (%) | ||
| White | 75 (48.4) | 76 (56.7) |
| Asian | 48 (31) | 35 (26.1) |
| Black | 2 (1.3) | 1 (0.7) |
| Other | 30 (19.4) | 22 (16.4) |
| Disease characteristics | TRUQAP + fulvestrant (n=155) | Placebo + fulvestrant (n=134) |
|---|---|---|
| Metastatic sites, n (%) | ||
| Bone only | 25 (16.1) | 16 (11.9) |
| Liver | 70 (45.2) | 53 (39.6) |
| Visceral | 103 (66.5) | 98 (73.1) |
| Endocrine resistance,* n (%) | ||
| Primary | 60 (38.7) | 55 (41) |
| Secondary | 95 (61.3) | 79 (59) |
- *Per ESO-ESMO guidelines: Primary endocrine resistance=relapse while on the first 2 years of adjuvant ET, or PD within first 6 months of 1L ET for mBC, while on ET. Secondary resistance=relapse while on adjuvant ET after the first 2 years, or relapse within 12 months of completing adjuvant ET, or PD ≥6 months after initiating ET for mBC, while on ET.3
| Prior treatments |
TRUQAP + fulvestrant (n=155) | Placebo + fulvestrant (n=134) |
|---|---|---|
| No. of prior ET for aBC, n (%) | ||
| 0 | 13 (8.4) | 20 (14.9) |
| 1 | 131 (84.5) | 96 (71.6) |
| 2 | 11 (7.1) | 18 (13.4) |
| Previous CDK4/6i, n (%) | ||
| Adjuvant/neoadjuvant | 0 | 2 (1.5) |
| aBC | 113 (72.9) | 91 (67.9) |
| Previous chemotherapy, n (%) | ||
| Adjuvant/neoadjuvant | 79 (51) | 67 (50) |
| aBC | 30 (19.4) | 23 (17.2) |
| Alterations2 | TRUQAP + fulvestrant (n=155) | Placebo + fulvestrant (n=134) |
|---|---|---|
| PIK3CA,* n (%) | 116 (74.8) | 103 (76.9) |
| AKT1 (only), n (%) | 18 (11.6) | 15 (11.2) |
| PTEN (only), n (%) | 21 (13.5) | 16 (11.9) |
- †Includes 58 (16.3%) patients in the TRUQAP + fulvestrant arm and 48 (13.6%) in the placebo + fulvestrant arm with unknown status.4
76%
of patients with alterations in CAPItello-291 had a PIK3CA alteration1,2
How TRUQAP works
Explore efficacy
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.
