Zie ook in gerelateerde artikelen hiernaast of hieronder

Capivasertib (merknaam Truqap) is ook een effectief medicijn bij hormoongevoelige borstkanker zie dit artikel

2 juli 2026: Bron: ESMO Annals of Oncology

Wanneer Capivasertib (merknaam Truqap) wordt toegevoegd aan Abiraterone bij patiënten met uitgezaaide hormoongevoelige prostaatkanker en met aangetoonde PTEN deficiëntie = gebrek en/of gedeeltelijk of geheel ontbreken van het gen Fosfatase- en Tensinehomoloog dan verbetert de door scans aangetoonde ziekteprogressievrije overleving met mediaan 7,5 maanden - van 27.7 naar 33.2 maanden - in vergelijking met alleen Abiraterone plus hormoontherapie. Dat blijkt uit de placebo gecontroleerde gerandomiseerde fase III studie CAPitello-281

De resultaten uit het abstract vertaalt:

  • 25,3% (1519/6003) van de patiënten met geldige tumortestresultaten had PTEN-deficiënte tumoren. In de gerandomiseerde PTEN-deficiënte populatie werd een statistisch significante verbetering van de rPFS waargenomen met Capivasertib plus Abiraterone (n = 507, mediaan 33,2 maanden) versus placebo plus Abiraterone [n = 505, 25,7 maanden; hazard ratio (HR) 0,81, 95% betrouwbaarheidsinterval (BI) 0,66-0,98, P = 0,034].
  • Post-hoc rPFS-analyses voor PTEN-verliesdrempelwaarden van ≥95%, ≥99% en 100% toonden aan dat de groep met Capivasertib plus Abiraterone consistent presteerde over de verschillende drempelwaarden, terwijl de groep met placebo plus Abiraterone progressief slechter presteerde naarmate de drempelwaarde voor de mate van PTEN-verlies werd verhoogd, wat resulteerde in een numeriek verbeterd behandelingseffect.
  • In de totale onderzochte populatie was de HR voor OS (26,4% volwassenheid) 0,90, 95% CI 0,71-1,15, P = 0,401.
  • De meest voorkomende bijwerkingen (AE's) voor Capivasertib plus Abiraterone waren diarree (51,9%; 8,0% placebo plus Abiraterone), hyperglykemie (38,0%; 12,9%) en huiduitslag (35,4%; 7,0%).
  • Sterfgevallen als gevolg van een bijwerking werden gemeld bij 36 (7,2%) en 26 (5,2%) patiënten in respectievelijk de Capivasertib plus Abiraterone- en de placebo plus Abiraterone groep.

Conclusies:

Capivasertib plus Abiraterone verbetert de rPFS ten opzichte van placebo plus Abiraterone bij PTEN-deficiënte mHSPC = uitgezaaide hormoongevoelige prostaatkanker, in combinatie met ADT = hormoontherapie, met een mediane verbetering van de rPFS = met scans aangetoonde ziekteprogressievrije overleving met 7,5 maanden. Het bijwerkingenprofiel was consistent met dat van de afzonderlijke middelen. Patiënten met PTEN-deficiënte mHSPC profiteren van de dubbele blokkade van de PI3K/AKT- en AR-routes met Capivasertib plus Abiraterone.

Het volledige studieverslag is gratis in te ziein PDF formaat. Klik daarvoor op de titel van het abstract:

Original articleVolume 37, Issue 1p53-68January 2026Open access

Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study

Affiliations & Notes
1Department of Cancer Medicine, Institut Gustave Roussy, Centre Oscar Lambret, University of Paris Saclay, Villejuif, France
2The Christie and Salford Royal NHS Foundation Trusts, University of Manchester, Manchester, UK
3Charite Universitätsmedizin Berlin, Berlin, Germany
4Medical University of Vienna, Vienna, Austria
5Kindai University Hospital, Osaka, Japan
6Hospital Nora Teixeira and PUCRS School of Medicine, Porto Alegre, Brazil
7SBU Gulhane Training and Research Hospital, Ankara, Turkey
8Szpital Wojewódzki w Koszalinie, Koszalin, Poland
9Hospital Universitario Central de Asturias, Oviedo, Spain
10Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
11Hunan Cancer Hospital, Hunan, China
12Hospital Maria Auxiliadora, Lima, Peru
13Derriford Hospital, Plymouth, UK
14Mater Hospital Brisbane, Mater Misericordiae Ltd, Brisbane, Australia
15Mater Clinical Unit, School of Clinical Medicine, The University of Queensland, Brisbane, Australia
16Kyungpook National University Chilgok Hospital, Daegu, South Korea
17Fudan University Shanghai Cancer Center, Shanghai, China
18Bravis Ziekenhuis, Roosendaal, The Netherlands
19Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
20AstraZeneca, Cambridge, UK
21AstraZeneca, Barcelona, Spain
22AstraZeneca, Gaithersburg, USA
23Duke University Cancer Institute, Durham, USA
Note: This study was presented at the ESMO Congress 2025, 17-21 October 2025, Berlin, Germany.
A list of the members of the CAPItello-281 Study Group is provided in the Supplementary Appendix, available at https://doi.org/10.1016/j.annonc.2025.10.004.
Article Info
Publication History:
Published online October 19, 2025
Copyright: © 2025 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.
Cover Image - Annals of Oncology, Volume 37, Issue 1

Highlights

Patients with PTEN-deficient mHSPC received capivasertib or placebo + abiraterone, prednisone/prednisolone and ADT.
Capivasertib + abiraterone showed a statistically significant rPFS benefit vs placebo + abiraterone.
Post-hoc analyses at higher PTEN deficiency cut-offs showed increasing treatment benefit with capivasertib + abiraterone.
Capivasertib + abiraterone safety profile was consistent with their individual drug profiles.
Patients with PTEN-deficient mHSPC clinically benefit from combined AKT and AR inhibition with capivasertib + abiraterone.

Abstract

Background

In metastatic hormone-sensitive prostate cancer (mHSPC), phosphatase and tensin homolog (PTEN) deficiency results in phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway activation, providing an independent proliferative drive, which cannot be suppressed by androgen receptor pathway inhibitors (ARPIs), resulting in worse outcomes. Dual inhibition of PI3K/AKT and AR pathways with capivasertib and abiraterone may delay progression and improve disease outcomes.

Patients and methods

In CAPItello-281 (NCT04493853), patients with PTEN-deficient mHSPC (diagnostic cut-off: ≥90% viable malignant cells with no specific cytoplasmic PTEN immunohistochemistry staining) received capivasertib or placebo (1 : 1) plus abiraterone, prednisone/prednisolone, and androgen deprivation therapy (ADT). The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS); overall survival (OS) was a key secondary endpoint. Post hoc exploratory subgroups at increasing PTEN cut-off thresholds were also assessed.

Results

25.3% (1519/6003) of patients with valid tumor test results had PTEN-deficient tumors. In the randomized PTEN-deficient population, a statistically significant improvement in rPFS was observed with capivasertib plus abiraterone (n = 507, median 33.2 months) versus placebo plus abiraterone [n = 505, 25.7 months; hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.66-0.98, P = 0.034]. Post hoc rPFS analyses for loss of PTEN cut-offs of ≥95%, ≥99%, and 100% showed that the capivasertib plus abiraterone arm performed consistently across cut-offs, but the placebo plus abiraterone arm performed progressively worse as the cut-off for the degree of PTEN loss was increased, resulting in a numerically improved treatment effect. In the overall population studied, the HR for OS (26.4% maturity) was 0.90, 95% CI 0.71-1.15, P = 0.401. The most common adverse events (AEs) for capivasertib plus abiraterone were diarrhea (51.9%; 8.0% placebo plus abiraterone), hyperglycemia (38.0%; 12.9%), and rash (35.4%; 7.0%). Deaths associated with an AE were reported in 36 (7.2%) and 26 (5.2%) patients in the capivasertib plus abiraterone and placebo plus abiraterone arms, respectively.

Conclusions

Capivasertib plus abiraterone improves rPFS versus placebo plus abiraterone in PTEN-deficient mHSPC, on a background of ADT, with a 7.5-month improvement in median rPFS. AE profile was consistent with that of the individual agents. Patients with PTEN-deficient mHSPC benefit from dual blockade of the PI3K/AKT and AR pathways with capivasertib plus abiraterone.


Acknowledgements

We thank all the patients and their families, all the investigators, trial-site coordinators and nurses, and the members of the independent data and safety monitoring committee. Medical writing assistance was provided by Martin Goulding, DPhil, from AMICULUM Business Services Limited, funded by AstraZeneca. Capivasertib was discovered by AstraZeneca after a collaboration with Astex Therapeutics Limited (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Funding

This work was supported by AstraZeneca (no grant number).

Disclosure

KF reports institutional honoraria or payments to Gustave Roussy Institute from Astellas, AstraZeneca, Bayer, Janssen, Merck Sharpe & Dohme (MSD), Novartis, and Sanofi; institutional participation on data safety monitoring or advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis, Pfizer, and Sanofi; and personal participation on a data safety monitoring or advisory board for Arvinas, CureVac, Macrogenics, and Orion. NWC reports receiving institutional consultancy or advisory fees from Astellas Pharma, Bayer, Ferring, Janssen-Cilag, and Sanofi; speaker bureau fees from Astellas Pharma, AstraZeneca, Bayer, Janssen-Cilag, Pfizer, and Sanofi; and travel and accommodation expenses associated with lectures and advisory board meetings from Astellas Pharma, AstraZeneca, Bayer, Ferring, Ipsen, Janssen-Cilag, and Sanofi. MDS reports consulting fees and payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Gilead, Immunomedics, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, Seagen, and Thermosome. MK reports payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from AstraZeneca, MSD, and Novartis; and support for attending meetings and/or travel from MSD. CAF reports consulting fees, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, Bayer, Merck, and Pfizer; and support for attending meetings and/or travel from Ipsen, Pfizer, and Roche. MS reports acting in a consultancy or advisory role for Adium, BMS, Johnson and Johnson, and in a speaking role for AstraZeneca, Johnson and Johnson, MSD, Pfizer and Roche. NO reports educational support and consulting/advisory board fees from AstraZeneca, Astellas, Bayer, BMS, Daiichi Sankyo, GSK, Ipsen Biopharm Limited, Johnson & Johnson, Merck/Pfizer, MSD, and The Limbic. PD reports honoraria from Astellas Pharma, Bristol Myers Squibb, Janssen, Merck Sharp & Dohme, and Roche; consulting or advisory role for Astellas Pharma, Bristol Myers Squibb, Eisai, Janssen, Merck Sharp & Dohme, and Roche; speakers’ bureau for Amgen, Astellas, BioPharma, Bristol Myers Squibb, Eisai, Janssen, Merck Sharp & Dohme, and Roche; and research funding from Janssen, Merck Sharp & Dohme, and Roche. CR, CG, MYV, and JL were AstraZeneca employees and shareholders at the time of study. DJG reports grants from Calithera, Convergence, and Corvus; grants and personal fees from Astellas, Bristol Myers Squibb, Johnson and Johnson Pharmaceuticals, Merck Sharp & Dohme, Novartis, and Pfizer; personal fees from AstraZeneca, Axess Oncology, Capio Bioscience, Flatiron, Michael J Hennessey Associates, Millennium Medical Publishing, Myovant Sciences Inc, NCI Genitourinary, Nektar Therapeutics, Physician Education Resource, Platform Q, Propella Therapeutics, RevHealth, Seattle Genetics, UroGPO, Vizuri Health Sciences, WebMD, and Xcures; grants, personal fees, and non-financial support from Bayer Healthcare Pharmaceuticals, and Exelixis Inc; personal fees and non-financial support from UroToday; and other support from the American Association for Cancer Research, all outside of the submitted work. All other authors have declared no conflicts of interest.

Data sharing

Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://www.astrazenecaclinicaltrials.com/our-transparency-commitments/. Data for studies directly listed on Vivli can be requested through Vivli at https://www.vivli.org. Data for studies not listed on Vivli can be requested through Vivli at https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/. AstraZeneca’s Vivli member page outlines further details: https://vivli.org/ourmember/astrazeneca/.

Supplementary data (1)

Supplementary Data

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