Drug Update · Oncology

FDA Approves Capivasertib for PTEN‑Deficient mAPMN/S: 7.5‑mo rPFS

July 12, 2026

Primary endpoint (rPFS)

Median 33.2 vs 25.7 months (HR 0.81; 95% CI 0.66-0.98; P = 0.034) [1]

Median rPFS improvement

7.5 months (capivasertib plus abiraterone vs placebo plus abiraterone) [1]

Randomized PTEN‑deficient population

n = 507 (capivasertib) and n = 505 (placebo) [1]

Selected safety signals (trial)

Diarrhea 51.9% vs 8.0%; Hyperglycemia 38.0% vs 12.9%; Rash 35.4% vs 7.0%; AE‑related deaths 7.2% vs 5.2% [1]

FDA approval date (label revision)

June 12, 2026 (label update/indication) [6][12]

Clinical Perspective

This approval affects medical oncologists and urologic oncology clinicians treating adult patients with newly diagnosed metastatic androgen pathway modulation‑naïve or ‑sensitive prostate cancer who have tumors that are PTEN‑deficient as detected by an FDA‑authorized test ^[2]^[1]. The CAPItello‑281 data support dual blockade of the PI3K/AKT and androgen receptor pathways with capivasertib plus abiraterone and prednisone on a background of ADT, producing a 7.5‑month median rPFS improvement versus placebo plus abiraterone in PTEN‑deficient patients ^[1]^[2]. Key practical considerations include selecting patients by validated PTEN testing and proactive baseline and interval glucose and dermatologic monitoring given the known risks of hyperglycemia, diarrhea, and cutaneous adverse reactions ^[2]^[1].

Dr. Rahul Verma · Oncology

The FDA approved capivasertib (TRUQAP) in combination with abiraterone and prednisone for adult patients with metastatic androgen pathway modulation‑naïve or ‑sensitive (mAPMN/S) prostate cancer that is PTEN‑deficient on June 12, 2026, based on CAPItello‑281 showing investigator‑assessed radiographic progression‑free survival (rPFS) median 33.2 months versus 25.7 months (HR 0.81; 95% CI 0.66–0.98; P = 0.034) versus placebo plus abiraterone ^[2]^[1]. The approval and labeling update specify selection by PTEN deficiency as detected by an FDA‑authorized test and the recommended combination regimen with abiraterone and prednisone ^[2]^[3].

Clinical Context

Capivasertib (TRUQAP) is an oral small‑molecule AKT inhibitor that targets AKT1, AKT2 and AKT3 and inhibits phosphorylation of downstream AKT substrates, interrupting PI3K/AKT pathway signaling implicated in tumors with PTEN loss or activating PI3K/AKT alterations ^[4]^[2]. AstraZeneca markets TRUQAP; the U.S. prescribing information lists indications in HR‑positive, HER2‑negative breast cancer (with PIK3CA/AKT1/PTEN alterations) and now PTEN‑deficient mAPMN/S prostate cancer detected by an FDA‑authorized test ^[2]^[4]. The FDA‑authorized label requires selection of patients on the basis of PTEN deficiency and provides dosing and monitoring guidance for combination use with abiraterone and prednisone ^[2]^[3]. CAPItello‑281 was used to support the prostate cancer indication ^[1]^[2].

Key Findings

The randomized CAPItello‑281 trial enrolled 1,012 patients with newly diagnosed PTEN‑deficient mAPMN/S prostate cancer defined centrally (diagnostic cut‑off: ≥90% viable malignant cells with no specific cytoplasmic PTEN staining) and randomized patients 1:1 to capivasertib plus abiraterone versus placebo plus abiraterone on a background of androgen deprivation therapy ^[1]. In the randomized PTEN‑deficient population, investigator‑assessed rPFS was median 33.2 months with capivasertib plus abiraterone (n = 507) versus 25.7 months with placebo plus abiraterone (n = 505); the hazard ratio was 0.81 (95% CI 0.66–0.98; P = 0.034) ^[1]. The trial report notes a 7.5‑month improvement in median rPFS in the capivasertib arm and states that post hoc analyses across stricter PTEN loss cut‑offs showed a consistent effect with a numerically larger treatment effect as the degree of PTEN loss increased ^[1]. Overall survival was a key secondary endpoint; at 26.4% maturity the OS HR in the overall population was 0.90 (95% CI 0.71–1.15; P = 0.401) ^[1]. CAPItello‑281’s positive rPFS result formed the efficacy basis for the FDA approval of TRUQAP in PTEN‑deficient mAPMN/S prostate cancer ^[1]^[2].

Safety & Tolerability

The most common adverse events reported with capivasertib plus abiraterone were diarrhea (51.9% versus 8.0% with placebo plus abiraterone) ^[1].
Hyperglycemia was reported in 38.0% of patients receiving capivasertib plus abiraterone versus 12.9% with placebo plus abiraterone; the label warns that TRUQAP can cause severe hyperglycemia including diabetic ketoacidosis and fatal outcomes and recommends baseline and interval glucose monitoring ^[1]^[2].
Rash was reported in 35.4% of patients with capivasertib plus abiraterone versus 7.0% with placebo plus abiraterone ^[1].
Deaths associated with an adverse event occurred in 36 (7.2%) patients in the capivasertib plus abiraterone arm and 26 (5.2%) in the placebo plus abiraterone arm in the trial report ^[1].

Study Design

CAPItello‑281 was a randomized, double‑blind, placebo‑controlled, multicenter phase III trial enrolling 1,012 adult patients with centrally confirmed PTEN‑deficient mAPMN/S prostate cancer (PTEN diagnostic cut‑off ≥90% viable malignant cells with no specific cytoplasmic staining) ^[1]. Patients were randomized 1:1 to capivasertib plus abiraterone, prednisone and ADT versus placebo plus abiraterone, prednisone and ADT. The primary endpoint was investigator‑assessed radiographic progression‑free survival (rPFS); overall survival was a key secondary endpoint ^[1]. Randomized PTEN‑deficient populations were n = 507 (capivasertib) and n = 505 (placebo) for the primary analysis ^[1].

FAQ

Q1 What is capivasertib (TRUQAP) approved for?

Capivasertib (TRUQAP) is approved in combination with abiraterone and prednisone for the treatment of adult patients with metastatic androgen pathway modulation‑naïve or ‑sensitive (mAPMN/S) prostate cancer that is PTEN‑deficient as detected by an FDA‑authorized test. The approval also retains TRUQAP’s breast cancer indication for HR‑positive, HER2‑negative disease with PIK3CA/AKT1/PTEN alterations; for the prostate cancer indication selection by PTEN deficiency was required for patient eligibility.

Q2 How does capivasertib work?

Capivasertib is an oral inhibitor of all three AKT isoforms (AKT1, AKT2, AKT3) that inhibits phosphorylation of downstream AKT substrates and suppresses PI3K/AKT pathway signaling. AKT pathway activation can result from PTEN loss and other upstream alterations; preclinical models showed capivasertib activity in PTEN‑deficient prostate cancer models and enhanced antitumor activity when combined with androgen‑pathway inhibitors such as abiraterone.

Q3 What is the recommended dose of capivasertib for this indication?

The recommended dosing schedule of TRUQAP in the approved prostate cancer indication is 400 mg orally twice daily, given for 4 days followed by 3 days off each week, in combination with abiraterone and prednisone; continue until disease progression or unacceptable toxicity. Patients should be selected based on PTEN deficiency in tumor tissue as detected by an FDA‑authorized test. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects to monitor?

Across CAPItello‑281 and the U.S. label, clinicians should monitor for diarrhea, hyperglycemia (including severe hyperglycemia and diabetic ketoacidosis), and cutaneous adverse reactions, which were among the most frequent adverse events. In CAPItello‑281 diarrhea occurred in 51.9% of patients receiving capivasertib plus abiraterone versus 8.0% with placebo plus abiraterone; hyperglycemia occurred in 38.0% versus 12.9%, and rash occurred in 35.4% versus 7.0%. Deaths associated with an adverse event were reported in 36 (7.2%) patients on capivasertib plus abiraterone and 26 (5.2%) on placebo plus abiraterone in the trial report. The label includes detailed recommendations for baseline and interval fasting glucose and HbA1c testing and guidance for dose modifications for hyperglycemia, diarrhea, and cutaneous reactions.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Capivasertib for PTEN‑Deficient mAPMN/S: 7.5‑mo rPFS

FDA Approves Capivasertib for PTEN‑Deficient mAPMN/S: 7.5‑mo rPFS

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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