Announcement • Jun 13

Astrazeneca TRUQAP Combination Approves in the US as First and Only Targeted Treatment for PTEN-Deficient Metastatic Hormone-Sensitive Prostate Cancer

AstraZeneca’s TRUQAP (capivasertib) in combination with abiraterone and prednisone has been approved in the US as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC), as detected by a US Food and Drug Administration (FDA)-authorized test. The approval by the US FDA was based on positive results from the CAPItello-281 Phase III trial, presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in Annals of Oncology. Results from the primary analysis of the CAPItello-281 Phase III trial showed a statistically significant 19% reduction in the risk of radiographic disease progression or death and a clinically meaningful improvement in median radiographic progression-free survival (rPFS) of 7.5 months with TRUQAP in combination with abiraterone and androgen deprivation therapy (ADT) versus treatment with abiraterone and ADT with placebo (based on a hazard ratio [HR] of 0.81; 95% confidence interval [CI] 0.66–0.98; p=0.034). Median rPFS was 33.2 months for the TRUQAP combination versus 25.7 months for the comparator arm. While overall survival (OS) data were immature at the time of the primary analysis, results for OS numerically favored the TRUQAP combination versus the comparator arm. The trial will continue as planned to further assess OS as a key secondary endpoint. The safety profile of TRUQAP in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine. Grade 3 or higher adverse events occurred in 67% of patients treated with the TRUQAP combination, with rash (12.3%) and hyperglycemia (10.3%) the most frequently reported. Concurrently with this approval, the FDA also approved a companion diagnostic test to detect PTEN deficiency in tumors of patients with prostate adenocarcinoma. A regulatory application for the TRUQAP combination in this setting is under review in the EU based on the CAPItello-281 Phase III trial. TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. TRUQAP can cause severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes. In CAPItello-281, increased fasting glucose (FG) from baseline occurred in 69% of patients treated with TRUQAP, including 25% of patients with Grade 2 (FG >160 to 250 mg/dL), 12% with Grade 3 (FG >250 to 500 mg/dL), and 1.2% of patients with Grade 4 (FG >500 mg/dL) events. The median time to first occurrence of hyperglycemia was 71 days (range: 1 to 1454). Dose reduction for hyperglycemia was required in 8.7% of patients and permanent discontinuation was required in 2.4% of patients. Diabetic ketoacidosis occurred in 1.2% of patients. In the study, 41% (204/503) of patients who received TRUQAP had an anti-hyperglycemic medication regimen either initiated or changed, including treatment with insulin in 16% (81/503) of patients. The safety of TRUQAP has not been established in patients with Type 1 diabetes or Type 2 diabetes that is uncontrolled or requiring insulin at baseline as these patients were excluded from clinical studies. Before initiating treatment with TRUQAP, test fasting glucose levels (FPG or FBG), 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. Withhold TRUQAP in clinical situations known to increase the risk of severe hyperglycemia or ketoacidosis (eg, suspected serious infection or acute illness). Based on the severity of hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP. TRUQAP can cause severe diarrhea associated with dehydration. In CAPItello-281, diarrhea of any grade occurred in 264 (52%) patients. Grade 3 occurred in 31 (6%) patients and Grade 4 occurred in 1 (0.2%) patient. The median time to first occurrence was 12 days (range: 3 to 48). In the study, dose reductions were required in 26 (5%) patients and 6 (1.2%) patients discontinued TRUQAP due to diarrhea. In the 264 patients with diarrhea, anti-diarrheal medication was required in 64% (170/264) of patients to manage diarrhea symptoms. Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start anti-diarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. TRUQAP can cause cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia (PPE), and drug reaction with eosinophilia and systemic symptoms (DRESS). In CAPItello-281, cutaneous adverse reactions occurred in 53% of patients. Grade 3 cutaneous adverse reactions occurred in 84 (17%) patients and Grade 4 occurred in 1 (0.2%) patients. The median time to onset of rash was 13 days (range: 11 to 63 days). In the study, dose reduction was required in 58 (12%) patients and 38 (8%) patients discontinued TRUQAP due to rash. Among the 265 patients with cutaneous adverse reactions, 80% (212/265) required treatment and 91% (242/265) recovered in the study. Of these, 54% (115/212) were treated with topical corticosteroids and 25% (54/212) with systemic corticosteroids. Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. Based on findings from animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman.

AstraZeneca PLC Stock Price

AZN Share Price Performance

AZN Community Narratives

AZN: In-Market Oncology And U.S. Drug Pricing Will Shape Long-Term Performance

Increasing Regulatory Controls And Patent Expiries Will Erode Value

Aging, Emerging Markets And Precision Medicine Will Unlock Secular Growth

AZN: In-Market Oncology And U.S. Drug Pricing Will Shape Long-Term Performance

Aging, Emerging Markets And Precision Medicine Will Unlock Secular Growth

Increasing Regulatory Controls And Patent Expiries Will Erode Value

Trending Discussion

Recently Updated Narratives

AZN: New Approvals And AI Use Will Support Future Repricing

AZN: Updated Oncology Pipeline Outlook Will Support Multi Year Re Rating

AZN: 1H26 Trial Cluster Will Test Sustained Premium Earnings Expectations

Snowflake Analysis

AstraZeneca PLC Key Details

About AZN

Recent AZN News & Updates

AstraZeneca (LSE:AZN) Stock Could Be 20.2% Below Fair Value After Recent Pullback

AZN: New Approvals And AI Use Will Support Future Repricing

Astrazeneca TRUQAP Combination Approves in the US as First and Only Targeted Treatment for PTEN-Deficient Metastatic Hormone-Sensitive Prostate Cancer

Recent updates

AstraZeneca PLC Competitors

GSK

Haleon

Hikma Pharmaceuticals