The US Food and Drug Administration (FDA) has approved capivasertib (Truqap) in combination with abiraterone and prednisone as the first and only targeted treatment for adult patients with PTEN-deficient metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer, as detected by an FDA-authorised companion diagnostic test. The approval, granted on 12 June 2026, is supported by results from the CAPItello-281 Phase III trial and marks the entry of this first-in-class AKT inhibitor into a second tumour type.

Clinical Takeaway

✔ Capivasertib plus abiraterone/prednisone is now the first and only targeted therapy approved for PTEN-deficient mAPMN/S prostate cancer, a biomarker-defined subgroup representing approximately one in four patients with this stage of disease.

✔ PTEN deficiency can be identified by immunohistochemistry (IHC) at the time of diagnosis, and a companion diagnostic has been concurrently approved to identify eligible patients.

✔ Median radiographic progression-free survival (rPFS) improved by 7.5 months (33.2 vs. 25.7 months) with the capivasertib combination versus abiraterone plus ADT alone.

Drug Profile & Mechanism

  • Drug name: Capivasertib (brand name: Truqap), developed by AstraZeneca
  • Drug class: First-in-class, oral AKT inhibitor
  • Mechanism: Capivasertib inhibits AKT, a key kinase in the PI3K/AKT/mTOR signalling pathway. Loss of PTEN function leads to constitutive activation of this pathway, promoting tumour cell survival and proliferation. By blocking AKT, capivasertib counteracts the oncogenic signalling driven by PTEN deficiency.
  • Combination regimen: Capivasertib is administered with abiraterone (an androgen biosynthesis inhibitor) and prednisone, together with androgen deprivation therapy (ADT)
  • Prior approval: Capivasertib was previously approved in combination with fulvestrant for HR-positive, HER2-negative breast cancer with certain PIK3CA/AKT1/PTEN alterations, making prostate cancer its second approved tumour type

Target Population

  • Approved indication: Adult patients with PTEN-deficient mAPMN/S prostate cancer (previously referred to as metastatic hormone-sensitive prostate cancer [mHSPC] or metastatic castration-sensitive prostate cancer [mCSPC]), as detected by an FDA-authorised test
  • Nomenclature update: The term mAPMN/S reflects newly redefined regulatory and clinical trial terminology for this disease stage; oncologists should be aware that this replaces the older mHSPC/mCSPC labels in regulatory contexts
  • Global burden: Approximately 200,000 patients worldwide are diagnosed with mAPMN/S prostate cancer annually, including approximately 35,000 in the US
  • PTEN-deficient subset: Approximately one in four mAPMN/S patients harbour PTEN-deficient tumours, equating to roughly 50,000 patients globally and ~8,750 in the US per year
  • Prognostic significance of PTEN deficiency: PTEN loss fuels cancer cell growth, defines a particularly aggressive disease phenotype, and is an independent risk factor for poor outcomes regardless of other clinical characteristics; it can be identified by IHC testing at diagnosis

Study Design: CAPItello-281

  • Trial name: CAPItello-281
  • Phase: Phase III, randomised, placebo-controlled
  • Patient population: Adult patients with PTEN-deficient mAPMN/S prostate cancer; PTEN deficiency was prospectively defined as part of the trial design
  • Treatment arms:
    • Experimental arm: Capivasertib + abiraterone + ADT
    • Control arm: Placebo + abiraterone + ADT
  • Data presentation: Primary results were presented at the 2025 ESMO Congress and published in Annals of Oncology

Endpoints

  • Primary endpoint: Radiographic progression-free survival (rPFS) — defined as time to radiographic disease progression or death
  • Key secondary endpoint: Overall survival (OS) — data were immature at the time of the primary analysis; the trial will continue to assess OS

Efficacy Outcomes

  • rPFS — Capivasertib combination: Median 33.2 months
  • rPFS — Control arm: Median 25.7 months
  • Absolute improvement in median rPFS: 7.5 months
  • Risk reduction: 19% reduction in the risk of radiographic disease progression or death (HR 0.81; 95% CI 0.66–0.98; p=0.034)
  • Statistical significance: The primary endpoint was met with a statistically significant result
  • Overall survival: OS data were immature at the primary analysis; results numerically favored the capivasertib combination; further OS follow-up is ongoing

Safety

  • The safety profile of capivasertib in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each individual agent
  • Grade ≥3 adverse events: Occurred in 67% of patients treated with the capivasertib combination
  • Most frequently reported Grade ≥3 adverse events:
    • Rash: 12.3%
    • Hyperglycaemia: 10.3%
  • Clinicians should monitor patients for dermatological toxicity and glucose dysregulation, which are established class effects associated with AKT inhibition

Companion Diagnostic

Concurrently with the approval of capivasertib, the FDA approved a companion diagnostic test to detect PTEN deficiency in tumour tissue from patients with prostate adenocarcinoma. PTEN deficiency can be identified by IHC at the time of diagnosis, enabling prospective biomarker-driven patient selection. Oncologists should ensure PTEN testing is incorporated into routine diagnostic workup for patients with newly diagnosed mAPMN/S prostate cancer to identify those eligible for this targeted combination therapy.

Regulatory Status

  • US FDA: Approved 12 June 2026 for PTEN-deficient mAPMN/S prostate cancer
  • European Union: A regulatory application for capivasertib in this setting is currently under review by the European Medicines Agency (EMA), based on the CAPItello-281 Phase III trial data

Key Clinical Implications

✔ PTEN testing should become standard practice at diagnosis in patients with mAPMN/S prostate cancer; approximately 25% will harbour PTEN-deficient tumours and may benefit from this targeted approach.

✔ Capivasertib plus abiraterone/prednisone/ADT offers the first biomarker-directed treatment option in the hormone-sensitive/androgen pathway-naïve setting, addressing a population with a historically poor prognosis and limited targeted options.

✔ A 7.5-month improvement in median rPFS (33.2 vs. 25.7 months) represents a clinically meaningful delay in disease progression for a patient group characterised by faster progression and worse outcomes compared to PTEN-intact disease.

✔ Oncologists should be aware of the updated mAPMN/S nomenclature, which replaces mHSPC and mCSPC terminology in regulatory and clinical trial contexts, and should familiarise themselves with this terminology for patient communication and documentation.

✔ Proactive monitoring for rash and hyperglycaemia (the most common Grade ≥3 toxicities) is essential, and appropriate supportive care protocols should be in place prior to initiating capivasertib-based therapy.

✔ Overall survival data remain immature; longer-term follow-up from CAPItello-281 is ongoing and will be critical to establishing the full magnitude of benefit with this combination.

Bottom Line

The FDA approval of capivasertib (Truqap) in combination with abiraterone and prednisone establishes the first targeted, biomarker-driven treatment option for patients with PTEN-deficient mAPMN/S prostate cancer — a subgroup defined by aggressive disease biology and historically poor outcomes. Supported by a statistically significant improvement in rPFS from the CAPItello-281 Phase III trial, this approval underscores the growing importance of routine PTEN biomarker testing at diagnosis to identify patients most likely to benefit. With an EU regulatory review underway, the capivasertib combination has the potential to reshape the treatment landscape for this molecularly defined prostate cancer subpopulation on a global scale.

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